Substituted polycyclic aryl and heteroaryl uracils useful for selective inhibition of the coagulation cascade

ABSTRACT

The invention relates to substituted polycyclic aryl and heteroaryl uracil compounds useful as inhibitors of serine proteases of the coagulation cascade and compounds, compositions and methods for anticoagulant therapy for the treatment and prevention of a variety of thrombotic conditions including coronary artery and cerebrovascular diseases.

FIELD OF THE INVENTION

[0001] This invention is in the field of anticoagulant therapy, andspecifically relates to compounds, compositions and methods forpreventing and treating thrombotic conditions such as coronary arteryand cerebrovascular disease. More particularly, the invention relates tosubstituted polycyclic aryl and heteroaryl uracil compounds that inhibitserine proteases of the coagulation cascade.

BACKGROUND OF THE INVENTION

[0002] Physiological systems control the fluidity of blood in mammals[Majerus, P. W. et al: Anticoagulant, Thrombolytic, and AntiplplateletDrugs. In Hardman, J. G. and Limbird, L. E., editors: Goodman & Gilman'sThe Pharmacological Basis of Therapeutics. 9th edition. New York,McGraw-Hill Book Co., 1996, pp. 1341-1343]. Blood must remain fluidwithin the vascular systems and yet be able to undergo hemostasis,cessation of blood loss from a damaged vessel, quickly. Hemostasis orclotting begins when platelets first adhere to macromolecules insubendothelian regions of an injured and/or damaged vessels. Theseplatelets aggregate to form the primary hemostatic plug and stimulatelocal activation of plasma coagulation factors leading to generation ofa fibrin clot that reinforces the aggregated platelets.

[0003] Plasma coagulation factors include factors II, V, VII, VIII, IX,X, XI, and XII; these are also called protease zymogens. Thesecoagulation factors or protease zymogens are activated by serineproteases leading to coagulation in a so called “coagulation cascade” orchain reaction [Handin, R. I.: Bleeding and Thrombosis. In Wilson, J.,et al. editors: Harrison's Principles of Internal Medicine. 12thEdition, New York, McGraw-Hill Book Co., 1991,p.350]. Coagulation orclotting occurs in two ways through different pathways. An intrinsic orcontact pathway leads from XII to XIIa to XIa to IXa and to theconversion of X to Xa. Xa with factor Va converts prothrombin (II) tothrombin (IIa) leading to conversion of fibrinogen to fibrin.Polymerization of fibrin leads to a fibrin clot. An extrinsic pathway isinitiated by the conversion of coagulation factor VII to VIIa by Xa. Thepresence of Tissue Factor and VIIa accelerates formation of Xa in thepresence of calcium ion and phospholipids. Formation of Xa leads tothrombin, fibrin, and a fibrin clot as described above. The presence ofone or more of these many different coagulation factors and two distinctpathways of clotting could enable the efficacious, selective control andbetter understanding of parts of the coagulation or clotting process.

[0004] While clotting as a result of an injury to a blood vessel is acritical physiological process for mammals such as man, clotting canalso lead to disease states. A pathological process called thrombosisresults when platelet aggregation and/or a fibrin clot blocks (i.e.,occludes) a blood vessel. Arterial thrombosis may result in ischemicnecrosis of the tissue supplied by the artery. When the thrombosisoccurs in a coronary artery, a myocardial infarction or heart attack canresult. A thrombosis occurring in a vein may cause tissues drained bythe vein to become edematous and inflamed. Thrombosis of a deep vein maybe complicated by a pulmonary embolism. Preventing or treating clots ina blood vessel may be therapeutically useful by inhibiting formation ofblood platelet aggregates, inhibiting formation of fibrin, inhibitingthrombus formation, inhibiting embolus formation, and for treating orpreventing unstable angina, refractory angina, myocardial infarction,transient ischemic attacks, atrial fibrillation, thrombotic stroke,embolic stroke, deep vein thrombosis, disseminated intravascularcoagulation, ocular build up of fibrin, and reocclusion or restenosis ofrecanalized vessels.

[0005] There have been several reports of non-peptidic and peptidicuracil compounds that act as an inhibitor of a coagulation factorpresent in the coagulation cascade or clotting process. In U.S. Pat. No.5,656,645, Tamura et al. describe4,5,6-substituted-3-aminopyridonyl-acetamides, 1,6-substituted-5-aminouracinylacetamides, and2,4-substituted-5-aminopyrimidinonyl-acetamides in which the amidesubstituents all have a formyl group and which reportedly have activityagainst thrombin. In U.S. Pat. No. 5,658,930, Tamura et al. againdescribe 4,5,6-substituted-3-aminopyridonyl-acetamides, 1,6-substituted-5-aminouracinylacetamides, and2,4-substituted-5-amino-pyrimidinonylacetamides in which the amidesubstituents all have a formyl group and which reportedly have activityagainst thrombin. In PCT Patent Applications 96/18644 and 97/46207,Tamura et al. further describe 4,5,6-substituted-3-aminopyridonylacetamides, 1,6-substituted-5-aminouracinyl-acetamides,and 2,4-substituted-5-amino-pyrimidinonylacetamides in which the amidesubstituents all have a formyl group and which reportedly have activityagainst thrombin.

SUMMARY OF THE INVENTION

[0006] It is an object of the present invention to provide compoundsthat are beneficial in anticoagulant therapy and that have a generalstructure:

[0007] It is another object of the present invention to provide methodsfor preventing and treating thrombotic conditions, such as coronaryartery disease, cerebrovascular disease, and other coagulation relateddisorders. Such thrombotic conditions are prevented and treated byadministering to a patient in need thereof an effective amount ofcompounds of Formula (I).

[0008] Various other objects and advantages of the present inventionwill become apparent from the following description of the invention.

DESCRIPTION OF THE INVENTION

[0009] The present invention relates to a class of compounds comprisingSubstituted Polycyclic Aryl and Heteroaryl uracils, which are beneficialin anticoagulant therapy for the treatment and prevention of a varietyof thrombotic conditions including coronary artery and cerebrovasculardisease, as given in Formula (I):

[0010] or a pharmaceutically acceptable salt thereof, wherein;

[0011] J^(a) and J^(b) are independently selected from the groupconsisting of O and S;

[0012] J^(a) is optionally selected from the group consisting of CH—R⁶and N—R⁶ wherein R⁶ is a linear spacer moiety having from 1 through 4contiguous atoms linked to the point of bonding of a substituentselected from the group consisting of R^(4a), R^(4b), R¹⁴, R¹⁵, R³⁹,R⁴⁰, and R⁵ to form a heterocyclyl ring having 5 through 8 contiguousmembers;

[0013] J^(b) is optionally selected from the group consisting of CH—R⁶and N—R⁶ wherein R⁶ is a linear spacer moiety having from 1 through 4contiguous atoms linked to the point of bonding of a substituentselected from the group consisting of R₁, R^(4a), R^(4b), R¹⁴ and R¹⁵ toform a heterocyclyl ring having 5 through 8 contiguous members;

[0014] J^(a) and J^(b) are optionally independently selected from thegroup consisting of CH—R⁶ and N—R⁶ wherein R⁶ is a linear spacer moietyhaving from 1 through 4 contiguous atoms linked to the points of bondingof both R^(4a) and R^(4b) to form a heterocyclyl ring having 5 through 8contiguous members;

[0015] J^(a) is optionally selected from the group consisting of CH—R⁶and N—R⁶ wherein R⁶ is a linear spacer moiety having from 1 through 4contiguous atoms linked to the points of bonding of both R³⁹ and R⁴⁰ toform a heterocyclyl ring having 5 through 8 contiguous members;

[0016] B is formula (V):

[0017]  wherein D¹, D², J¹, J² and K¹ are independently selected fromthe group consisting of C, N, O, S and a covalent bond with the provisosthat no more than one can be a covalent bond, no more than one of D¹,D², J¹, J² and K¹ is O, no more than one of D¹, D², J¹, J² and K¹ is S,one of D¹, D², J¹, J² and K¹ must be a covalent bond when two of D¹, D²,J¹, J² and K¹ are O and S, and no more than four of D¹, D², J¹, J² andK¹ are N with the proviso that R³², R³³, R³⁴, R³⁵, and R³⁶ are eachindependently selected to maintain the tetravalent nature of carbon,trivalent nature of nitrogen, the divalent nature of sulfur, and thedivalent nature of oxygen;

[0018] R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁶, R¹⁷, R¹⁸, R¹⁹, R³², R³³, R³⁴, R³⁵,and R³⁶ are independently selected from the group consisting of hydrido,acetamido, haloacetamido, amidino, guanidino, dialkylsulfonium,trialkylphosphonium, dialkylsulfoniumalkyl, carboxy, heteroaralkylthio,heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aryloylalkoxy,heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl,heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl,aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl,cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl,cycloalkylsulfonylalkyl, heteroarylamino,N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio,alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy,cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy,cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy,halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl,hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio,alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl,heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl,arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl,heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl,haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido,alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, monoarylamidosulfonyl, arylsulfonamido,diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl,arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl,heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl,heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl,alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy,cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl,lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy,hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, alkylenylamino,hydroxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy,aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl,heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl,heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl,carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido,arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboxy,carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy,phosphono, phosphonoalkyl, diaralkoxyphosphono, anddiaralkoxyphosphonoalkyl;

[0019] R¹⁶, R¹⁹, R³², R³³, R³⁵ and R³⁶ are independently optionallyQ^(b) with the proviso that no more than one of R¹⁶ and R¹⁹ is Q^(b) atthe same time and that Q^(b) is Q^(be);

[0020] R³² and R³³, R³³ and R³⁴, R³⁴ and R³⁵, and R³⁵ and R³⁶ areindependently optionally selected to form a spacer pair wherein a spacerpair is taken together to form a linear moiety having from 3 through 6contiguous atoms connecting the points of bonding of said spacer pairmembers to form a ring selected from the group consisting of acycloalkenyl ring having 5 through 8 contiguous members, a partiallysaturated heterocyclyl ring having 5 through 8 contiguous members, aheteroaryl ring having 5 through 6 contiguous members, and an aryl withthe proviso that no more than one of the group consisting of spacerpairs R³² and R³³, R³³ and R³⁴, R³⁴ and R³⁵, and R³⁵ and R³⁶ are used atthe same time;

[0021] R⁹ and R¹⁰, R¹⁰ and R¹¹, R¹¹ and R¹², and R¹² and R¹³ areindependently optionally selected to form a spacer pair wherein a spacerpair is taken together to form a linear moiety having from 3 through 6contiguous atoms connecting the points of bonding of said spacer pairmembers to form a ring selected from the group consisting of acycloalkenyl ring having 5 through 8 contiguous members, a partiallysaturated heterocyclyl ring having 5 through 8 contiguous members, aheteroaryl ring having 5 through 6 contiguous members, and an aryl withthe proviso that no more than one of the group consisting of spacerpairs R⁹ and R¹⁰, R¹⁰ and R¹¹, R¹¹ and R¹², and R¹² and R¹³ are used atthe same time;

[0022] B is optionally formula (VI):

[0023]  wherein D³, D⁴, J³, J⁴ are independently selected from the groupconsisting of C, N, O, and S, no more than one of D³, D⁴, J³, and J⁴ isO, no more than one of D³, D⁴, J³, and J⁴ is S, and no more than threeof D¹, D², J¹, and J² are N with the proviso that R³², R³³, R³⁴, and R³⁵are each independently selected to maintain the tetravalent nature ofcarbon, trivalent nature of nitrogen, the divalent nature of sulfur, andthe divalent nature of oxygen;

[0024] B is optionally selected from the group consisting of hydrido,trialkylsilyl, C2-C8 alkyl, C3-C8 alkenyl, C3-C8 alkylehyl, C3-C8alkynyl, C2-C8 haloalkyl, and C3-C8 haloalkenyl wherein each member ofgroup B is optionally substituted at any carbon up to and including 6atoms from the point of attachment of B to A with one or more of thegroup consisting of R₃₂, R₃₃, R₃₄, R₃₅, and R₃₆;

[0025] B is optionally selected from the group consisting of C3-C15cycloalkyl, C5-C10 cycloalkenyl, C4-C12 saturated heterocyclyl, andC4-C9 partially saturated heterocyclyl, wherein each ring carbon isoptionally substituted with R³³, a ring carbon other than the ringcarbon at the point of attachment of B to A is optionally substitutedwith oxo provided that no more than one ring carbon is substituted byoxo at the same time, ring carbons and nitrogen adjacent to the carbonatom at the point of attachment are optionally substituted with R⁹ orR¹³, a ring carbon or nitrogen adjacent to the ^(R9) position and twoatoms from the point of attachment is optionally substituted with R¹⁰, aring carbon or nitrogen adjacent to the R¹³ position and two atoms fromthe point of attachment is optionally substituted with R¹², a ringcarbon or nitrogen three atoms from the point of attachment and adjacentto the R¹⁰ position is optionally substituted with R¹¹, a ring carbon ornitrogen atom three atoms from the point of attachment and adjacent tothe R¹² position is optionally substituted with R³³, and a ring carbonor nitrogen four atoms from the point of attachment and adjacent to theR¹¹ and R³³ positions is optionally substituted with R³⁴;

[0026] A is selected from the group consisting of single covalent bond,(W⁷)_(rr)—(CH(R¹⁵))_(pa) and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is aninteger selected from 0 through 1, pa is an integer selected from 0through 6, and W⁷ is selected from the group consisting of O, S, C(O),C(S), C(O)S, C(S)O, C(O)N(R⁷), C(S)N(R⁷), (R⁷)NC(O), (R⁷)NC(S), S(O),S(O)₂, S(O)₂N(R⁷), (R⁷)NS(O)₂, Se(O), Se(O)₂, Se(O)₂N(R⁷), (R⁷)NSe(O)₂,P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), C(NR⁷)N(R⁷), (R⁷)NC(NR⁷),(R⁷)NC(NR⁷)NR⁷, and N(R⁷) with the proviso that no more than one of thegroup consisting of rr and pa is 0 at the same time;

[0027] R⁷ and R⁸ are independently selected from the group consisting ofhydrido, hydroxy, alkyl, alkenyl, aryl, aralkyl, aryloxy, alkoxy,alkenyloxy, alkylthio, alkylamino, arylthio, arylamino, acyl, aroyl,heteroaroyl, aralkoxyalkyl, heteroaralkoxyalkyl, aryloxyalkyl,alkoxyalkyl, alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl,aralkoxyalkyl, heteroaralkoxyalkyl, alkylsulfinylalkyl,alkylsulfonylalkyl, heteroaryl, heteroaryloxy, heteroarylamino,heteroaralkyl, heteroaralkyloxy, heteroaralkylamino, andheteroaryloxyalkyl;

[0028] R¹⁴, R¹⁵, R³⁷, R³⁸, R⁴⁰, R⁴¹ and R⁴² are independently selectedfrom the group consisting of amidino, hydroxyamino, hydrido, hydroxy,halo, cyano, aryloxy, amino, alkylamino, dialkylamino, hydroxyalkyl,aminoalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, sulfhydryl,acylamido, alkoxy, alkylthio, arylthio, alkyl, alkenyl, alkynyl, aryl,aralkyl, aryloxyalkyl, aralkoxyalkylalkoxy, alkylsulfinylalkyl,alkylsulfonylalkyl, aralkylthioalkyl, heteroaralkoxythioalkyl,alkoxyalkyl, heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl,arylthioalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl,cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl,halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl,halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl,saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl,heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl,monocarboalkoxyalkyl, dicarboalkoxyalkyl, monocyanoalkyl, dicyanoalkyl,carboalkoxycyanoalkyl, alkylsulfinyl, alkylsulfonyl, haloalkylsulfinyl,haloalkylsulfonyl, arylsulfinyl, arylsulfinylalkyl, arylsulfonyl,arylsulfonylalkyl, aralkylsulfinyl, aralkylsulfonyl, cycloalkylsulfinyl,cycloalkylsulfonyl, cycloalkylsulfinylalkyl, cycloalkylsufonylalkyl,heteroarylsulfonylalkyl, heteroarylsulfinyl, heteroarylsulfonyl,heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl,carboxy, carboxyalkyl, carboalkoxy, carboxamide, carboxamidoalkyl,carboaralkoxy, trialkylsilyl, dialkoxyphosphono, diaralkoxyphosphono,dialkoxyphosphonoalkyl, and diaralkoxyphosphonoalkyl with the provisothat R³⁷ and R³⁸ are independently selected from other than formyl;

[0029] R¹⁴ and R¹⁴, when bonded to different carbons, are optionallytaken together to form a group selected from the group consisting ofcovalent bond, alkylene, haloalkylene, and a linear moiety spacerselected to form a ring selected from the group consisting of cycloalkylring having from 5 through 8 contiguous members, cycloalkenyl ringhaving from 5 through 8 contiguous members, and a heterocyclyl havingfrom 5 through 8 contiguous members;

[0030] R¹⁴ and R¹⁵, when bonded to different carbons, are optionallytaken together to form a group selected from the group consisting ofcovalent bond, alkylene, haloalkylene, and a linear moiety spacerselected to form a ring selected from the group consisting of acycloalkyl ring having from 5 through 8 contiguous members, acycloalkenyl ring having from 5 through 8 contiguous members, and aheterocyclyl having from 5 through 8 contiguous members;

[0031] R¹⁵ and R¹⁵, when bonded to different carbons, are optionallytaken together to form a group selected from the group consisting ofcovalent bond, alkylene, haloalkylene, and a linear moiety spacerselected to form a ring selected from the group consisting of cycloalkylring having from 5 through 8 contiguous members, cycloalkenyl ringhaving from 5 through 8 contiguous members, and a heterocyclyl havingfrom 5 through 8 contiguous members;

[0032] Ψ is selected from the group consisting of NR⁵, O, C(O), C(S), S,S(O), S(O)₂, ON(R⁵), P(O)(R⁸), and CR³⁹R⁴⁰;

[0033] R⁵ is selected from the group consisting of hydrido, hydroxy,amino, alkyl, alkenyl, alkynyl, aryl, aralkyl, aryloxy, aralkoxy,alkoxy, alkenyloxy, alkylthio, arylthio, aralkoxyalkyl,heteroaralkoxyalkyl, aryloxyalkyl, alkoxyalkyl, alkenyloxyalkyl,alkylthioalkyl, arylthioalkyl, aralkoxyalkyl, heteroaralkoxyalkyl,alkylsulfinylalkyl, alkylsulfonylalkyl, cycloalkyl, cycloalkylalkyl,cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl, haloalkyl,haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl,haloalkenyloxyalkyl, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl,heteroaryl, heteroarylalkyl, monocarboalkoxyalkyl, monocarboalkoxy,dicarboalkoxyalkyl, monocarboxamido, monocyanoalkyl, dicyanoalkyl,carboalkoxycyanoalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, anddialkoxyphosphonoalkyl;

[0034] R³⁹ and R⁴⁰, when bonded to the same carbon, are optionally takentogether to form a group selected from a group consisting of oxo,thiono, R⁵—N, alkylene, haloalkylene, and a linear moiety spacer havingfrom 2 through 7 contiguous atoms to form a ring selected from the groupconsisting of a cycloalkyl ring having from 3 through 8 contiguousmembers, a cycloalkenyl ring having from 3 through 8 contiguous members,and a heterocyclyl ring having from 3 through 8 contiguous members;

[0035] M is selected from the group consisting of N and R¹—C;

[0036] R² and R¹ are independently selected from the group consisting ofZ⁰—Q, hydrido, alkyl, alkenyl, and halo;

[0037] R¹ is optionally selected from the group consisting of amino,aminoalkyl, alkylamino, amidino, guanidino, hydroxy, hydroxyamino,alkoxy, hydroxyalkyl, alkoxyamino, thiol, alkylthio, dialkylsulfonium,trialkylphosphonium, dialkylsulfoniumalkyl, heteroarylamino, nitro,arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl,aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl, cyano, andphosphono;

[0038] R² is optionally selected from the group consisting of amidino,guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl,heteroarylamino, amino, nitro, alkylamino, arylamino, aralkylamino,alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl,haloalkanoyl, hydroxyhaloalkyl, cyano, and phosphono;

[0039] R² and R^(4a), R² and R^(4b), R² and R¹⁴, and R² and R¹⁵ areoptionally independently selected to form spacer pairs wherein a spacerpair is taken together to form a linear moiety having from 2 through 5contiguous atoms connecting the points of bonding of said spacer pairmembers to form a heterocyclyl ring having from 5 through 8 contiguousmembers with the proviso that no more than one of the group of spacerpairs consisting of R² and R^(4a), R² and R^(4b), R² and R¹⁴ and R² andR¹⁵ is used at the same time;

[0040] R² is optionally independently selected to form a linear moietyhaving from 2 through 5 contiguous atoms linked to the points of bondingof both R^(4a) and R^(4b) to form a heterocyclyl ring having from 5through 8 contiguous members;

[0041] Z⁰ is selected from the group consisting of covalent single bond,(CR⁴¹R⁴²)_(q) wherein q is an integer selected from 1 through 6,(CH(R⁴¹))_(g)—W⁰—(CH(R⁴²))_(p) wherein g and p are integersindependently selected from 0 through 3 and W⁰ is selected from thegroup consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,C(O)N(R⁴¹), (R⁴¹)NC(O), C(S)N(R⁴¹), (R⁴¹)NC(S), OC(O)N(R⁴¹),(R⁴¹)NC(O)O, SC(S)N(R⁴¹), (R⁴¹)NC(S)S, SC(O)N(R⁴¹), (R⁴¹)NC(O)S,OC(S)N(R⁴¹), (R⁴¹)NC(S)O, N(R⁴²)C(O)N(R⁴¹), (R⁴¹)NC(O)N(R⁴²),N(R⁴²)C(S)N(R⁴¹), (R⁴¹)NC(S)N(R⁴²), S(O), S(O)₂, S(O)₂N(R⁴¹),N(R⁴¹)S(O)₂, Se, Se(O), Se(O)₂, Se(O)₂N(R⁴¹), N(R⁴¹)Se(O)₂, P(O)(R⁸),N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R⁴¹), ON(R⁴¹), and SiR²⁸R²⁹, and(CH(R⁴¹))_(e)—W²²—(CH(R⁴²))_(h) wherein e and h are integersindependently selected from 0 through 2 and W²² is selected from thegroup consisting of CR⁴¹═CR⁴², CR⁴¹R⁴²═C; vinylidene), ethynylidene(C═C; 1,2-ethynyl), 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl,1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl,2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl,1,2-piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl, 2,6-piperazinyl,1,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,2,6-piperidinyl, 3,4-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl,2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, and3,4-tetrahydrofuranyl, with the provisos that R⁴¹ and R⁴² are selectedfrom other than halo and cyano when directly bonded to N and Z⁰ isdirectly bonded to the uracil ring;

[0042] R²⁸ and R²⁹ are independently selected from the group consistingof hydrido, hydroxyalkyl, alkyl, alkenyl, alkynyl, aryl, aralkyl,aryloxyalkyl, acyl, aroyl, aralkanoyl, heteroaroyl, aralkoxyalkyl,alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl,heteroaralkylthioalkyl, alkoxyalkyl, heteroaryloxyalkyl,alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl,cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl,haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl,haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxy,halocycloalkoxyalkyl, halocycloalkenyloxyalkyl, perhaloaryl,perhaloaralkyl, perhaloaryloxyalkyl, heteroaryl, heteroarylalkyl,heteroarylthioalkyl, heteroaralkylthioalkyl, cyanoalkyl, dicyanoalkyl,carboxamidoalkyl, dicarboxamidoalkyl, cyanocarboalkoxyalkyl,carboalkoxyalkyl, dicarboalkoxyalkyl, cyanocycloalkyl,dicyanocycloalkyl, carboxamidocycloalkyl, dicarboxamidocycloalkyl,carboalkoxycyanocycloalkyl, carboalkoxycycloalkyl,dicarboalkoxycycloalkyl, formylalkyl, acylalkyl, arylsulfinylalkyl,arylsulfonylalkyl, aralkylsulfinyl, cycloalkylsulfinylalkyl,cycloalkylsufonylalkyl, heteroarylsulfonylalkyl,heteroarylsulfinylalkyl, aralkylsulfinylalkyl, aralkylsulfonylalkyl,carboxy, dialkoxyphosphono, diaralkoxyphosphono, dialkoxyphosphonoalkyland diaralkoxyphosphonoalkyl;

[0043] R²⁸ and R²⁹ are optionally taken together to form a linear moietyspacer having from 2 through 7 contiguous atoms and forming a ringselected from the group consisting of a cycloalkyl ring having from 3through 8 contiguous members, a cycloalkenyl ring having from 3 through8 contiguous members, and a heterocyclyl ring having from 3 through 8contiguous members;

[0044] Q is formula (II):

[0045]  wherein D¹, D², J¹, J² and K¹ are independently selected fromthe group consisting of C, N, O, S and a covalent bond with the provisosthat no more than one can be a covalent bond, no more than one of D¹,D², J¹, J² and K¹ can be O, no more than one of D¹, D², J¹, J² and K¹can be S, one of D¹, D², J¹, J² and K¹ must be a covalent bond when twoof D¹, D², J¹, J² and K¹ are O and S, and no more than four of D¹, D²,J¹, J² and K¹ can be N, with the proviso that R⁹, R¹⁰, R¹¹, R¹², and R¹³are each independently selected to maintain the tetravalent nature ofcarbon, trivalent nature of nitrogen, the divalent nature of sulfur, andthe divalent nature of oxygen;

[0046] Q is optionally selected from formula (III):

[0047]  wherein D³, D⁴, J³, and J⁴ are independently selected from thegroup consisting of C, N, O, and S, no more than one of D³, D⁴, J³, andJ⁴ is O, no more than one of D³, D⁴, J³, and J⁴ is S, and no more thanthree of D¹, D², J¹, and J² are N with the proviso that R⁹, R¹⁰, R¹¹,and R¹² are each independently selected to maintain the tetravalentnature of carbon, trivalent nature of nitrogen, the divalent nature ofsulfur, and the divalent nature of oxygen;

[0048] Q is optionally selected from the group consisting of hydrido,alkyl, alkoxy, alkylamino, alkylthio, haloalkylthio, alkenyl, alkynyl,saturated heterocyclyl, partially saturated heterocyclyl, acyl, aroyl,heteroaroyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl,cycloalkenylalkyl, cycloalkylalkenyl, haloalkyl, haloalkoxy,haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl,haloalkenyloxyalkyl, halocycloalkoxyalkyl, and halocycloalkenyloxyalkylwith the proviso that Z⁰ is selected from other than a single covalentbond when Q is hydrido;

[0049] K is (CR^(4a)R^(4b))_(n) wherein n is an integer selected from 1through 4;

[0050] R^(4a) and R^(4b) are independently selected from the groupconsisting of halo, hydrido, hydroxy, cyano, hydroxyalkyl, alkyl,alkenyl, aryl, aralkyl, aralkoxyalkyl, aryloxyalkyl, alkoxyalkyl,heteroaryloxyalkyl, alkenyloxyalkyl, alkylthioalkyl, aralkylthioalkyl,arylthioalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, haloalkenyl,heteroaryl, heteroarylalkyl, heteroarylthioalkyl,heteroaralkylthioalkyl, cyanoalkyl, alkylsulfinylalkyl,alkylsulfonylalkyl, haloalkylsulfinyl, arylsulfinylalkyl,arylsulfonylalkyl, heteroarylsulfonylalkyl, heteroarylsulfinylalkyl,aralkylsulfinylalkyl, and aralkylsulfonylalkyl with the provisos thathalo, hydroxy, and cyano are bonded to different carbons whensimultaneously present and that R^(4a) and R^(4b) are other than hydroxyor cyano when bonded to the carbon directly bonded to the uracilnitrogen;

[0051] R^(4a) and R^(4b), when bonded to the same carbon, are optionallytaken together to form a group selected from the group consisting ofoxo, thiono, and a linear spacer moiety having from 2 through 7contiguous atoms connected to form a ring selected from the groupconsisting of a cycloalkyl ring having 3 through 8 contiguous members, acycloalkenyl ring having 5 through 8 contiguous members, and aheterocyclyl ring having 5 through 8 contiguous members with the provisothat R^(4a) and R^(4b) taken together is other than oxo or thiono whenthe common carbon is directly bonded to the uracil nitrogen;

[0052] E⁰ is E¹, when K is (CR^(4a)R^(4b))_(n), wherein E¹ is selectedfrom the group consisting of a covalent single bond, O, S, C(O), C(S),C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R⁷), (R⁷)NC(S),OC(O)N(R⁷), (R⁷)NC(O)O, SC(S)N(R⁷), (R⁷)NC(S)S, SC(O)N(R⁷), (R⁷)NC(O)S,OC(S)N(R⁷), (R⁷)NC(S)O, N(R⁸)C(O)N(R⁷), (R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷),(R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂, S(O)₂N(R⁷)C(O),C(O)N(R⁷)S(O)₂, Se, Se(O), Se(O)₂, Se(O)₂N(R⁷), N(R⁷)Se(O)₂, P(O)(R⁸),N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R⁷), ON(R⁷), SiR²⁸R²⁹, CR^(4a)═CR^(4b),ethynylidene (C═C; 1,2-ethynyl), and C═CR^(4a)R^(4b);

[0053] K is optionally selected to be (CH(R¹⁴))_(j)—T wherein j isselected from a integer from 0 through 3 and T is selected from thegroup consisting of single covalent bond, O, S, and N(R⁷) with theprovisos that R¹⁴ is other than hydroxy, cyano, halo, amino, alkylamino,dialkylamino, and sulfhydryl when j is 1 and that (CH(R¹⁴))_(j) isbonded to the uracil ring;

[0054] E⁰ is optionally E², when K is (CH(R¹⁴))_(j)—T, wherein E² isselected from the group consisting of a covalent single bond, C(O),C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R⁷),(R⁷)NC(S), (R⁷)NC(O)O, (R⁷)NC(S)S, (R⁷)NC(O)S, (R⁷)NC(S)O,N(R⁸)C(O)N(R⁷), (R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷), (R⁷)NC(S)N(R⁸), S(O),S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂, S(O)₂N(H)C(O), C(O)N(H)S(O)₂, Se(O),Se(O)₂, Se(O)₂N(R⁷), N(R⁷)Se(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸),P(O)(R⁸)N(R⁷), and N(R⁷);

[0055] K is optionally selected to be G—(CH(R¹⁵))_(k) wherein k isselected from an integer from 1 through 3 and G is selected from thegroup consisting of O, S, and N(R⁷) with the proviso that R¹⁵ is otherthan hydroxy, cyano, halo, amino, alkylamino, dialkylamino, andsulfhydryl when k is 1;

[0056] E⁰ is optionally E³ when K is G—(CH(R¹⁵))_(k) wherein E³ isselected from the group consisting of a covalent single bond, O, S,C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R⁷),(R⁷)NC(S), OC(O)N(R⁷), (R⁷)NC(O)O, SC(S)N(R⁷), (R⁷)NC(S)S, SC(O)N(R⁷),(R⁷)NC(O)S, OC(S)N(R⁷), (R⁷)NC(S)O, N(R⁸)C(O)N(R⁷), (R⁷)NC(O)N(R⁸),N(R⁸)C(S)N(R⁷), (R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂, Se,Se(O), Se(O)₂, Se(O)₂N(R⁷), N(R⁷)Se(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸),P(O)(R⁸)N(R⁷), N(R⁷), ON(R⁷), SiR²⁸R²⁹, CR^(4a)═CR^(4b), ethynylidene(C═C; 1,2-ethynyl), and C═CR^(4a)R^(4b);

[0057] Y⁰ is formula (IV):

[0058]  wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from thegroup consisting of C, N, O, S and a covalent bond with the provisosthat no more than one is a covalent bond, K² is independently selectedfrom the group consisting of C and N⁺, no more than one of D⁵, D⁶, J⁵,and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵, D⁶,J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶ are Oand S, no more than three of D⁵, D⁶, J⁵, and J⁶ are N when K² is N⁺, andno more than four of D⁵, D⁶, J⁵, and J⁶ are N when K² is carbon with theprovisos that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each independently selected tomaintain the tetravalent nature of carbon, trivalent nature of nitrogen,the divalent nature of sulfur, and the divalent nature of oxygen;

[0059] R¹⁶ and R¹⁷ are independently optionally taken together to form alinear moiety spacer having from 3 through 6 contiguous atoms connectedto form a ring selected from the group consisting of a cycloalkenyl ringhaving from 5 through 8 contiguous members, a partially saturatedheterocyclyl ring having from 5 through 8 contiguous members, aheteroaryl having from 5 through 6 contiguous members, and an aryl;

[0060] R¹⁸ and R¹⁹ are independently optionally taken together to form alinear moiety spacer having from 3 through 6 contiguous atoms connectedto form a ring selected from the group consisting of a cycloalkenyl ringhaving from 5 through 8 contiguous members, a partially saturatedheterocyclyl ring having from 5 through 8 contiguous members, aheteroaryl having from 5 through 6 contiguous members, and an aryl;

[0061] Q^(b) is selected from the group consisting of NR²⁰R²¹,⁺NR²⁰R²¹R²², oxy, alkyl, aminoalkylenyl, alkylamino, dialkylamino,dialkylsulfoniumalkyl, acylamino and Q^(be) wherein Q^(be) is hydridoand R²⁰, R²¹, and R²² are independently selected from the groupconsisting of hydrido, amino, alkyl, hydroxy, alkoxy, aminoalkylenyl,alkylamino, dialkylamino, and hydroxyalkyl with the provisos that nomore than one of R²⁰, R²¹, and R²² is hydroxy, alkoxy, alkylamino,amino, and dialkylamino at the same time and that R²⁰, R²¹, and R²² mustbe other than be hydroxy, alkoxy, alkylamino, amino, and dialkylaminowhen K² is N⁺;

[0062] R²⁰ and R²¹, R²⁰ and R²², and R²¹ and R²² are independentlyoptionally selected to form a spacer pair wherein a spacer pair is takentogether to form a linear moiety having from 4 through 7 contiguousatoms connecting the points of bonding of said spacer pair members toform a heterocyclyl ring having 5 through 8 contiguous members with theproviso that no more than one of the group consisting of spacer pairsR²⁰ and R²¹, R²⁰ and R²², and R²¹ and R²² is used at the same time;

[0063] Q^(b) is optionally selected from the group consisting ofN(R²⁶)SO₂N(R²³)(R²⁴), N(R²⁶)C(O)OR⁵, N(R²⁶)C(O)SR⁵, N(R²⁶)C(S)OR⁵ andN(R²⁶)C(S)SR⁵ with the proviso that no more than one of R²³, R²⁴, andR²⁶ can be hydroxy, alkoxy, alkyleneamino, alkylamino, amino, ordialkylamino when two of the group consisting of R²³, R²⁴, and R²⁶ arebonded to the same atom;

[0064] Q^(b) is optionally selected from the group consisting ofdialkylsulfonium, trialkylphosphonium, C(NR²⁵)NR²³R²⁴,N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)C(O)N(R²³)(R²⁴), N(R²⁶)C(S)N(R )(R²³)C(NR²⁵)OR⁵, C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), C(S)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), ON(R²⁶)C(NR²⁵)N(R²³)(R²⁴),N(R²⁶)N(R²⁶)SO₂N(R²³)(R²⁴), C(NR²⁵)SR⁵, C(O)NR²³R²⁴, and C(O)NR²³R²⁴with the provisos that no more than one of R²³, R²⁴, and R²⁶ can behydroxy, alkoxy, alkylamino, amino, or dialkylamino when any two of thegroup consisting of R²³, R²⁴, and R²⁶ are bonded to the same atom andthat said Q^(b) group is bonded directly to a carbon atom;

[0065] R²³, R²⁴, R²⁵, and R²⁶ are independently selected from the groupconsisting of hydrido, alkyl, hydroxy, alkoxy, alkylenylamino, amino,alkylamino, dialkylamino, and hydroxyalkyl;

[0066] R²³ and R²⁴ are optionally taken together to form a linear spacermoiety having from 4 through 7 contiguous atoms connecting the points ofbonding to form a heterocyclyl ring having 5 through 8 contiguousmembers;

[0067] R²³ and R²⁵, R²⁴ and R²⁵, R²⁵ and R²⁶, R²⁴ and R²⁶, and R²³ andR²⁶ are independently optionally selected to form a spacer pair whereina spacer pair is taken together from the points of bonding of selectedspacer pair members to form the group L—U—V wherein L, U, and V areindependently selected from the group consisting of O, S, C(O), C(S),C(J_(H))₂ S(O), SO₂, OP(OR³¹)R³⁰, P(O)R³⁰, P(S)R³⁰, C(R³⁰)R³¹,C═C(R³⁰)R³¹, (O)₂POP(O)₂, R³⁰(O)POP(O)R³⁰, Si(R²⁹)R²⁸, Si(R²⁹)R²⁸,Si(R²⁹)R²⁸, Si(R²⁹)R²⁸OSi(R²⁹)R²⁸, (R²⁸)R²⁹COC(R²⁸)R²⁹,(R²⁸)R²⁹CSC(R²⁸)R²⁹, C(O)C(R³⁰)═C(R³¹), C(S)C(R³⁰)═C(R³¹),S(O)C(R³⁰)═C(R³¹), SO₂C(R³⁰)═C(R³¹), PR³⁰C(R³⁰)═C(R³¹),P(O)R³⁰C(R³⁰)═C(R³¹), P(S)R³⁰C(R³⁰)═C(R³¹), DC(R³⁰)(R³¹)D, OP(OR³¹)R³⁰,P(O)R³⁰, P(S)R³⁰, Si(R²⁸)R²⁹ and N(R³⁰), and a covalent bond with theproviso that no more than any two of L, U and V are simultaneouslycovalent bonds and the heterocyclyl comprised of by L, U, and V has from5 through 10 contiguous member;

[0068] D is selected from the group consisting of oxygen, C═O, C═S,S(O)_(m) wherein m is an integer selected from 0 through 2;

[0069] J_(H) is independently selected from the group consisting ofOR²⁷, SR²⁷ and N(R²⁰)R²¹;

[0070] R²⁷ is selected from the group consisting of hydrido, alkyl,alkenyl, alkynyl, aralkyl, aryloxyalkyl, aralkoxyalkyl,alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl,heteroaralkylthioalkyl, alkoxyalkyl, heteroaryloxyalkyl,alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl,cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl,haloalkyl, haloalkenyl, halocycloalkyl, halocycloalkenyl,haloalkoxyalkyl, haloalkenyloxyalkyl, halocycloalkoxyalkyl,halocycloalkenyloxyalkyl, perhaloaryloxyalkyl, heteroaryl,heteroarylalkyl, heteroarylthioalkyl, heteroaralkylthioalkyl,arylsulfinylalkyl, arylsulfonylalkyl, cycloalkylsulfinylalkyl,cycloalkylsufonylalkyl, heteroarylsulfonylalkyl,heteroarylsulfinylalkyl, aralkylsulfinylalkyl and aralkylsulfonylalkyl;

[0071] R³⁰ and R³¹ are independently selected from the group consistingof hydrido, hydroxy, thiol, aryloxy, amino, alkylamino, dialkylamino,hydroxyalkyl, heteroaryloxyalkyl, alkoxy, alkylthio, arylthio, alkyl,alkenyl, alkynyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkyl,alkylsulfinylalkyl, alkylsulfonylalkyl, aralkylthioalkyl,heteroaralkoxythioalkyl, alkoxyalkyl, heteroaryloxyalkyl,alkenyloxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl,cycloalkylalkyl, cycloalkylalkenyl, cycloalkenyl, cycloalkenylalkyl,haloalkyl, haloalkenyl, haloaralkylsulfinylalkyl, aralkylsulfonylalkyl,cyanoalkyl, dicyanoalkyl, carboxamidoalkyl, dicarboxamidoalkyl,cyanocarboalkoxyalkyl, carboalkoxyalkyl, dicarboalkoxyalkyl,cyanocycloalkyl, dicyanocycloalkyl, carboxamidocycloalkyl,dicarboxamidocycloalkyl, carboalkoxycyanocycloalkyl,carboalkoxycycloalkyl, dicarboalkoxycycloalkyl, formylalkyl, acylalkyl,dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl, phosphonoalkyl,dialkoxyphosphonoalkoxy, diaralkoxyphosphonoalkoxy, phosphonoalkoxy,dialkoxyphosphonoalkylamino, diaralkoxyphosphonoalkylamino,phosphonoalkylamino, dialkoxyphosphonoalkyl, diaralkoxyphosphonoalkyl,sulfonylalkyl, alkoxysulfonylalkyl, aralkoxysulfonylalkyl,alkoxysulfonylalkoxy, aralkoxysulfonylalkoxy, sulfonylalkoxy,alkoxysulfonylalkylamino, aralkoxysulfonylalkylamino, andsulfonylalkylamino;

[0072] R³⁰ and R³¹ are optionally taken to form a linear moiety spacergroup having from 2 through 7 contiguous atoms to form a ring selectedfrom the group consisting of a cycloalkyl ring having from 3 through 8contiguous members, a cycloalkenyl ring having from 3 through 8contiguous members, and a heterocyclyl ring having from 3 through 8contiguous members;

[0073] R²³ and R²⁵, R²⁴ and R²⁵, R²⁵ and R²⁶, R²⁴ and R²⁶, and R²³ andR²⁶ are independently optionally selected to form a spacer pair whereina spacer pair is taken together from the points of bonding of selectedspacer pair members to form the group L—U—V wherein L, U, and V areindependently selected from the group of 1,2-disubstituted radicalsconsisting of a cycloalkyl radical, a cycloalkenyl radical whereincycloalkyl and cycloalkenyl radicals are substituted with one or moregroups selected from R³⁰ and R³¹, an aryl radical, an heteroarylradical, a saturated heterocyclic radical and a partially saturatedheterocyclic radical wherein said 1,2-substitutents are independentlyselected from C═O, C═S, C(R²⁸)R³², S(O), S(O)₂, OP(OR³¹)R³⁰, P(O)R³⁰,P(S)R³⁰ and Si(R²⁸)R²⁹;

[0074] R²³ and R²⁵, R²⁴ and R²⁵, R²⁵ and R²⁶, R²⁴ and R²⁶, and R²³ andR²⁶ are independently optionally selected to form a spacer pair whereina spacer pair is taken together from the points of bonding of selectedspacer pair members to form the group L—U—V wherein L, U, and V areindependently selected from the group of radicals consisting of1,2-disubstituted alkylene radicals and 1,2-disubstituted alkenyleneradical wherein said 1,2-substitutents are independently selected fromC═O, C═S, C(R²⁸)R²⁹, S(O), S(O)₂, OP(OR³¹)R³⁰, P(O)R³⁰, P(S)R³⁰, andSi(R²⁸)R²⁹ and said alkylene and alkenylene radical are substituted withone or more R³⁰ or R³¹ substituents;

[0075] Q^(s) is selected from the group consisting of a single covalentbond, (CR³⁷R³⁸)_(b)—(W⁰)_(az) wherein az is an integer selected from 0through 1, b is an integer selected from 1 through 4, and W⁰ is selectedfrom the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S,C(S)S, C(O)N(R¹⁴), (R¹⁴)NC(O), C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴),SC(S)N(R¹⁴), SC(O)N(R¹⁴), OC(S)N(R¹⁴), N(R¹⁵)C(O)N(R¹⁴),(R¹⁴)NC(O)N(R¹⁵), N(R¹⁵)C(S)N(R¹⁴), (R¹⁴)NC(S)N(R¹⁵), S(O), S(O)₂,S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, Se, Se(O), Se(O)₂, Se(O)₂N(R¹⁷), N(R¹⁴)Se(O)₂,P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R¹⁴), ON(R¹⁴), and SiR²⁸R²⁹,(CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d are integersindependently selected from 1 through 4, and W¹ is selected from thegroup consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,C(O)N(R¹⁴), (R¹⁴)NC(O), C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴),(R¹⁴)NC(O)O, SC(S)N(R¹⁴), (R¹⁴)NC(S)S, SC(O)N(R¹⁴), (R¹⁴)NC(O)S,OC(S)N(R¹⁴), (R¹⁴)NC(S)O, N(R¹⁵)C(O)N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵),N(R¹⁵)C(S)N(R¹⁴), (R¹⁴)NC(S)N(R¹⁵), S(O), S(O)₂, S(O)₂N(R¹⁴),N(R¹⁴)S(O)₂, Se, Se(O), Se(O)₂, Se(O)₂N(R¹⁴), N(R¹⁴)Se(O)₂, P(O)(R⁸),N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R¹⁴), ON(R¹⁴), SiR²⁸R²⁹, and(CH(R¹⁴))_(e)—W²²—(CH(R¹⁵))_(h) wherein e and h are integersindependently selected from 0 through 2 and W²² is selected from thegroup consisting of CR⁴¹═CR⁴², CR⁴¹R⁴²═C; vinylidene), ethynylidene(C═C; 1,2-ethynyl), 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl,1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl,2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5morpholinyl,1,2-piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl, 2,6-piperazinyl,1,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,2,6-piperidinyl, 3,4-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl,2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, and3,4-tetrahydrofuranyl, with the provisos that R¹⁴ and R¹⁵ are selectedfrom other than halo and cyano when directly bonded to N and that(CR³⁷R³⁸)_(b), (CH(R¹⁴))_(c), (CH(R¹⁴))_(e) and are bonded to E⁰;

[0076] R³⁷ and R³⁷, when bonded to different carbons, are optionallytaken together to form a linear moiety spacer having from 1 through 7contiguous atoms to form a ring selected from the group consisting of acycloalkyl ring having from 3 through 8 contiguous members, acycloalkenyl ring having from 3 through 8 contiguous members, and aheterocyclyl ring having from 3 through 8 contiguous members;

[0077] R³⁷ and R³⁸, when bonded to different carbons, are taken togetherto form a linear moiety spacer having from 1 through 7 contiguous atomsto form a ring selected from the group consisting of a cycloalkyl ringhaving from 3 through 8 contiguous members, a cycloalkenyl ring havingfrom 3 through 8 contiguous members, and a heterocyclyl ring having from3 through 8 contiguous members;

[0078] R³⁸ and R³⁸, when bonded to different carbons, are taken togetherto form a linear moiety spacer having from 1 through 7 contiguous atomsto form a ring selected from the group consisting of a cycloalkyl ringhaving from 3 through 8 contiguous members, a cycloalkenyl ring havingfrom 3 through 8 contiguous members, and a heterocyclyl ring having from3 through 8 contiguous members;

[0079] R³⁷ and R³⁸, when bonded to the same carbon, are taken togetherto form a group selected from a group consisting of oxo, thiono,alkylene, haloalkylene, and a linear moiety spacer having from 2 through7 contiguous atoms to form a ring selected from the group consisting ofa cycloalkyl ring having from 3 through 8 contiguous members, acycloalkenyl ring having from 3 through 8 contiguous members, and aheterocyclyl ring having from 3 through 8 contiguous members;

[0080] Y⁰ is optionally Q^(b)—Q^(ss) wherein Q^(ss) is selected from thegroup consisting of (CR³⁷R³⁸)_(f) wherein f is an integer selected from1 through 6, (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d are integersindependently selected from 1 through 4, and W¹ is selected from thegroup consisting of W¹ is selected from the group consisting of O, S,C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴), (R¹⁴)NC(O),C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴), (R¹⁴)NC(O)O, SC(S)N(R¹⁴),(R¹⁴)NC(S)S, SC(O)N(R¹⁴), (R¹⁴)NC(O)S, OC(S)N(R¹⁴), (R¹⁴)NC(S)O,N(R¹⁵)C(O)N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵), N(R¹⁵)C(S)N(R¹⁴), (R¹⁴)NC(S)N(R¹⁵),S(O), S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, Se, Se(O), Se(O)₂, Se(O)₂N(R¹⁴),N(R¹⁴)Se(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R¹⁴), ON(R¹⁴),SiR²⁸R²⁹, and (CH(R¹⁴))_(e)—W²—(CH(R¹⁵))_(h) wherein e and h areintegers independently selected from 0 through 2 and W² is selected fromthe group consisting of CR^(4a)═CR^(4b), ethynylidene (C≡C;1,2-ethynyl), and C═CR^(4a)R^(4b) with the provisos that R¹⁴ and R¹⁵ areselected from other than halo and cyano when directly bonded to N, that(CR³⁷R³⁸)_(f), (CH(R¹⁵))_(c), and (CH(R¹⁵))_(e) are bonded to E⁰, andQ^(b) is selected from other than N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴) orON(R²⁶)C(NR²⁵)N(R²³)(R²⁴) when Q^(ss) is (CR³⁷R³⁸)_(f) wherein f isother than the integer 1;

[0081] Y⁰ is optionally Q^(b)—Q^(sss) wherein Q^(sss) is(CH(R³⁸))_(r)—W³, r is an integer selected from 1 through 3, W³ isselected from the group consisting of 1,1-cyclopropyl, 1,2-cyclopropyl,1,1-cyclobutyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl,1,4-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl,2,4-morpholinyl, 2,5-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl,3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl,2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl,1,3-piperidinyl, 1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl,3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2H-2,3-pyranyl,2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H-2,4-pyranyl,4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl, 2H-pyran-2-one-4,5-yl,4H-pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl,2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl,3,4-tetrahydropyranyl, and 3,5-tetrahydropyranyl, and each carbon andhyrido containing nitrogen member of the ring of the W³ other than thepoints of attachment is optionally substituted with one or more of thegroup consisting of R⁹, R¹⁰, R¹¹, and R¹², with the proviso that(CH(R³⁸))_(r) is bonded to E⁰ and Q^(b) is bonded to lowest numberedsubstituent position of each W³;

[0082] Y⁰ is optionally Q^(b)—Q^(sssr) wherein Q^(sssr) is(CH(R³⁸))_(r)—W⁴, r is an integer selected from 1 through 3, W⁴ isselected from the group consisting of 1,2-cyclobutyl, 1,2-cyclohexyl,1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl,2,3-morpholinyl, 2,4-morpholinyl, 2,5-morpholinyl, 2,6-morpholinyl,3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl,1,4-piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl,1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl, 2,3-piperidinyl,2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl,3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl,2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl,4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl,2H-pyran-2-one-4,5-yl, 4H-pyran -4-one-2,3-yl, 2,3-tetrahydrofuranyl,2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl,2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl,2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl, and 3,5-tetrahydropyranyl,and each carbon and hydrido containing nitrogen member of the ring ofthe W⁴ other than the points of attachment is optionally substitutedwith one or more of the group consisting of R⁹, R¹⁰, R¹¹, and R¹², withthe provisos that (CH(R³⁸))_(r) is bonded to E⁰ and Q^(b) is bonded tohighest number substituent position of each W⁴;

[0083] Y⁰ is optionally Q^(b)—Q^(ssss) wherein Q^(ssss) is(CH(R³⁸))_(r)—W⁵, r is an integer selected from 1 through 3, W⁵ isselected from the group consisting of 1,4-indenyl, 1,5-indenyl,1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl,2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl,2,4-benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl,3,4-benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-imidazo(1,2-a)pyridinyl,2,5-imidazo (1,2-a)pyridinyl, 2,6-imidazo(1,2-a)pyridinyl,2,7-imidazo(1,2-a)pyridinyl, 3,4-imidazo(1,2-a)pyridinyl,3,5-imidazo(1,2-a)pyridinyl, 3,6-imidazo (1,2-a)pyridinyl,3,7-imidazo(1,2-a)pyridinyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl,2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl,1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl,2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl, 1,3-isoindolyl,3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl,2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl,3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl,3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl,1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl,2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl,3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl,3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl,4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl, and each carbon andhydrido containing nitrogen member of the ring of the W⁵ other than thepoints of attachment is optionally substituted with one or more of thegroup consisting of R⁹, R¹⁰, R¹¹, and R¹², with the proviso that Q^(b)is bonded to lowest number substituent position of each W⁵ and that(CH(R³⁸))_(r) is bonded to E⁰;

[0084] Y⁰ is optionally Q^(b)—Q^(ssssr) wherein Q^(ssssr) is(CH(R³⁸))_(r)—W⁶, r is an integer selected from 1 through 3, W⁶ isselected from the group consisting of 1,4-indenyl, 1,5-indenyl,1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl,2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl,2,4-benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl,3,4-benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,4-imidazo(1,2-a)pyridinyl,2,5-imidazo(1,2-a)pyridinyl, 2,6-imidazo(1,2-a)pyridinyl,2,7-imidazo(1,2-a)pyridinyl, 3,4-imidazo(1,2-a)pyridinyl,3,5-imidazo(1,2-a)pyridinyl, 3,6-imidazo(1,2-a)pyridinyl,3,7-imidazo(1,2-a)pyridinyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl,2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl,1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl, 2,4isoindolyl,2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl, 1,3-isoindolyl,3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl,2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl,3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl,3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl,1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl,2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4-quinolinyl,3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,4,5quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl,3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl,4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl, and each carbon andhydrido containing nitrogen member of the ring of the W⁶ other than thepoints of attachment is optionally substituted with one or more of thegroup consisting of R⁹, R¹⁰, R¹¹, and R¹², with the proviso that Q^(b)is bonded to highest number substituent position of each W⁶ and that(CH(R³⁸))_(r) is bonded to E⁰.

[0085] In an embodiment of compounds of Formula I or a pharmaceuticallyacceptable salt thereof,

[0086] J^(a) and J^(b) are independently selected from the groupconsisting of O and S;

[0087] B is formula (V):

[0088]  wherein D¹, D², J¹, J² and K¹ are independently selected fromthe group consisting of C, N, O, S and a covalent bond with the provisosthat no more than one is a covalent bond, no more than one of D¹, D²,J¹, J² and K¹ is O, no more than one of D¹, D², J¹, J² and K¹ is S, oneof D¹, D², J¹, J² and K¹ must be a covalent bond when two of D¹, D², J¹,J² and K¹ are O and S, and no more than four of D¹, D², J¹, J² and K¹are N with the proviso that R³², R³³, R³⁴, R³⁵, and R³⁶ are eachindependently selected to maintain the tetravalent nature of carbon,trivalent nature of nitrogen, the divalent nature of sulfur, and thedivalent nature of oxygen;

[0089] R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁶, R¹⁷, R¹⁸, R¹⁹, R³², R³³, R³⁴, R³⁵,and R³⁶ are independently selected from the group consisting of hydrido,acetamido, haloacetamido, amidino, guanidino, dialkylsulfonium,trialkylphosphonium, dialkylsulfoniumalkyl, carboxy, heteroaralkylthio,heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aryloylalkoxy,heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl,heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl,aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl,cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl,cycloalkylsulfonylalkyl, heteroarylamino,N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio,alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy,cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy,cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy,halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl,hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio,alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl,heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl,arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl,heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl,haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido,alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, monoarylamidosulfonyl, arylsulfonamido,diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl,arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl,heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl,heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl,alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy,cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl,lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy,hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, alkylenylamino,hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy,aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl,heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl,heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl,carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido,arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboxy,carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy,phosphono, phosphonoalkyl, diaralkoxyphosphono, anddiaralkoxyphosphonoalkyl;

[0090] R¹⁶, R¹⁹, R³², R³³, R³⁴, R³⁵, and R³⁶ are independentlyoptionally Q^(b) with the proviso that no more than one of R¹⁶ and R¹⁹is Q^(b) at the same time and that Q^(b) is Q^(be);

[0091] R³² and R³³, R³³ and R³⁴, R³⁴ and R³⁵, and R³⁵ and R³⁶ areindependently optionally selected to form a spacer pair wherein a spacerpair is taken together to form a linear moiety having from 3 through 6contiguous atoms connecting the points of bonding of said spacer pairmembers to form a ring selected from the group consisting of acycloalkenyl ring having 5 through 8 contiguous members, a partiallysaturated heterocyclyl ring having 5 through 8 contiguous members, aheteroaryl ring having 5 through 6 contiguous members, and an aryl withthe proviso that no more than one of the group consisting of spacerpairs R³² and R³³, R³³ and R³⁴, R³⁴ and R³⁵, and R³⁵ and R³⁶ can be usedat the same time;

[0092] R⁹ and R¹⁰, R¹⁰ and R¹¹, R¹¹ and R¹², and R¹² and R¹³ areindependently optionally selected to form a spacer pair wherein a spacerpair is taken together to form a linear moiety having from 3 through 6contiguous atoms connecting the points of bonding of said spacer pairmembers to form a ring selected from the group consisting of acycloalkenyl ring having 5 through 8 contiguous members, a partiallysaturated heterocyclyl ring having 5 through 8 contiguous members, aheteroaryl ring having 5 through 6 contiguous members, and an aryl withthe proviso that no more than one of the group consisting of spacerpairs R⁹ and R¹⁰, R¹⁰ and R¹¹, R¹¹ and R¹² and R¹³ can be used at thesame time;

[0093] B is optionally selected from the group consisting of hydrido,trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8alkynyl, C2-C8 haloalkyl, and C3-C8 haloalkenyl wherein each member ofgroup B may be optionally substituted at any carbon up to and including6 atoms from the point of attachment of B to A with one or more of thegroup consisting of R³², R³³, R³⁴, R³⁵, and R³⁶;

[0094] B is optionally selected from the group consisting of C3-C15cycloalkyl, C5-C10 cycloalkenyl, C4-C12 saturated heterocyclyl, andC4-C9 partially saturated heterocyclyl, wherein each ring carbon isoptionally substituted with R³³, a ring carbon other than the ringcarbon at the point of attachment of B to A is optionally substitutedwith oxo provided that no more than one ring carbon is substituted byoxo at the same time, ring carbons and a nitrogen adjacent to the carbonatom at the point of attachment are optionally substituted with R⁹ orR¹³, a ring carbon or nitrogen adjacent to the R⁹ position and two atomsfrom the point of attachment is optionally substituted with R¹⁰, a ringcarbon or nitrogen adjacent to the R¹³ position and two atoms from thepoint of attachment is optionally substituted with R¹², a ring carbon ornitrogen three atoms from the point of attachment and adjacent to theR¹⁰ position is optionally substituted with R¹¹, a ring carbon ornitrogen atom three from the point of attachment and adjacent to the R¹²position is optionally substituted with R³³, and a ring carbon ornitrogen four atoms from the point of attachment and adjacent to the R¹¹and R³³ positions is optionally substituted with R³⁴;

[0095] A is selected from the group consisting of single covalent bond,(W⁷)_(rr)—(CH(R¹⁵))_(pa) and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is aninteger selected from 0 through 1, pa is an integer selected from 0through 6, and W⁷ is selected from the group consisting of O, S, C(O),C(S), C(O)S, C(S)O, C(O)N(R⁷), C(S)N(R⁷), (R⁷)NC(O), (R⁷)NC(S), S(O),S(O)₂, S(O)₂N(R⁷), (R⁷)NS(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷),C(NR⁷)N(R⁷), (R⁷)NC(NR⁷), (R⁷)NC(NR⁷)NR⁷, and N(R⁷) with the provisothat no more than one of the group consisting of rr and pa can be 0 atthe same time;

[0096] R⁷ and R⁸ are independently selected from the group consisting ofhydrido, hydroxy, alkyl, acyl, aroyl, heteroaroyl, and alkoxyalkyl;

[0097] R¹⁴, R¹⁵, R³⁷, and R³⁸ are independently selected from the groupconsisting of hydrido, hydroxy, halo, cyano, hydroxyalkyl, alkoxy,alkyl, alkoxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl,cycloalkenylalkyl, haloalkyl, haloalkenyl, haloalkoxy, haloalkoxyalkyl,haloalkenyloxyalkyl, halocycloalkoxy, halocycloalkoxyalkyl,halocycloalkenyloxyalkyl, carboxy, carboxyalkyl, carboalkoxy,carboxamide, and carboxamidoalkyl;

[0098] R¹⁴ and R³⁸ can be independently selected from the groupconsisting of acyl, aroyl, and heteroaroyl with the proviso that acyl isselected from other than formyl;

[0099] Ψ is selected from the group consisting of NR⁵, O, C(O), C(S), S,S(O), S(O)₂, ON(R⁵), P(O)(R⁸), and CR³⁹R⁴⁰;

[0100] R⁵ is selected from the group consisting of hydrido, hydroxy,amino, alkyl, alkoxy, alkoxyalkyl, haloalkyl, acyl, aroyl, andheteroaroyl;

[0101] R³⁹ and R⁴⁰ are independently selected from the group consistingof hydrido, hydroxy, halo, cyano, hydroxyalkyl, acyl, aroyl,heteroaroyl, acylamido, alkoxy, alkyl, alkoxyalkyl, haloalkyl,haloalkoxy, haloalkoxyalkyl, alkylsulfonyl, haloalkylsulfonyl, carboxy,carboxyalkyl, carboalkoxy, carboxamide, and carboxamidoalkyl;

[0102] M is selected from the group consisting of N and R¹—C;

[0103] R² and R¹ are independently selected from the group consisting ofZ⁰—Q, hydrido, alkyl, alkenyl, and halo;

[0104] R¹ is optionally selected from the group consisting of amino,aminoalkyl, alkylamino, amidino, guanidino, hydroxy, hydroxyamino,alkoxy, hydroxyalkyl, alkoxyamino, thiol, alkylthio, dialkylsulfonium,trialkylphosphonium, dialkylsulfoniumalkyl, heteroarylamino, nitro,arylamino, aralkylamino, alkanoyl, alkenoyl, aroyl, heteroaroyl,aralkanoyl, heteroaralkanoyl, haloalkanoyl, hydroxyhaloalkyl, cyano, andphosphono;

[0105] Z⁰ is selected from the group consisting of covalent single bond,(CR⁴¹R⁴²)_(q) wherein q is an integer selected from 1 through 6,(CH(R⁴¹))_(g)—W⁰—(CH(R⁴²))_(p) wherein g and p are integersindependently selected from 0 through 3 and W⁰ is selected from thegroup consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S,C(O)N(R⁴¹), (R⁴¹)NC(O), C(S)N(R⁴¹), (R⁴¹)NC(S), OC(O)N(R⁴¹),(R⁴¹)NC(O)O, SC(S)N(R⁴¹), (R⁴¹)NC(S)S, SC(O)N(R⁴¹), (R⁴¹)NC(O)S,OC(S)N(R⁴¹), (R⁴¹)NC(S)O, N(R⁴²)C(O)N(R⁴¹), (R⁴¹)NC(O)N(R⁴²),N(R⁴²)C(S)N(R⁴¹), (R⁴¹)NC(S)N(R⁴²), S(O), S(O)₂, S(O)₂N(R⁴¹),N(R⁴¹)S(O)₂, Se, Se(O), Se(O)₂, Se(O)₂N(R⁴¹), N(R⁴¹)Se(O)₂, P(O)(R⁸),N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R⁴¹), ON(R⁴¹), and SiR²⁸R²⁹, and (CH(R⁴¹))_(e)—W²²—(CH(R⁴²))_(h) wherein e and h are integers independentlyselected from 0 through 2 and W²² selected from the group consisting ofCR⁴¹═CR⁴², CR⁴¹R⁴²═C; vinylidene), ethynylidene (C≡C; 1,2-ethynyl),1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl,1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl, 2,4-morpholinyl,2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl,1,3-piperazinyl, 2,3-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl,1,3-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl, 2,6-piperidinyl,3,4-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,2,3-tetrahydrofuranyl1, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl,and 3,4-tetrahydrofuranyl, with the provisos that R⁴¹ and R⁴² areselected from other than halo and cyano when directly bonded to N and Z⁰is directly bonded to the uracil ring;

[0106] R⁴¹ and R⁴² are independently selected from the group consistingof amidino, hydroxyamino, hydrido, hydroxy, amino, halo, cyano, aryloxy,hydroxyalkyl, acyl, aroyl, heteroaroyl, heteroaryloxyalkyl, alkoxy,alkyl, aryl, aralkyl, aryloxyalkyl, aralkoxyalkylalkoxy, alkoxyalkyl,heteroaryloxyalkyl, cycloalkyl, cycloalkylalkyl, cycloalkylalkenyl,cycloalkenyl, cycloalkenylalkyl, haloalkyl, haloalkenyl, halocycloalkyl,halocycloalkenyl, haloalkoxy, haloalkoxyalkyl, haloalkenyloxyalkyl,halocycloalkoxy, halocycloalkoxyalkyl, halocycloalkenyloxyalkyl,saturated heterocyclyl, partially saturated heterocyclyl, heteroaryl,heteroaralkyl, heteroarylthioalkyl, heteroaralkylthioalkyl,alkylsulfonyl, haloalkylsulfonyl, arylsulfonyl, arylsulfonylalkyl,aralkylsulfonyl, cycloalkylsulfonyl, cycloalkylsufonylalkyl,heteroarylsulfonylalkyl, heteroarylsulfonyl, and aralkylsulfonylalkyl;

[0107] Q is formula (II):

[0108]  wherein D¹, D², J¹, J² and K¹ are independently selected fromthe group consisting of C, N, O, S and a covalent bond with the provisosthat no more than one is a covalent bond, no more than one of D¹, D²,J¹, J² and K¹ is O, no more than one of D¹, D², J¹, J² and K¹ is S, oneof D¹, D², J¹, J² and K¹ must be a covalent bond when two of D¹, D², J¹,J² and K¹ are O and S, and no more than four of D¹, D², J¹, J² and K¹are N, with the proviso that R⁹, R¹⁰, R¹¹, R¹², and R¹³ are eachindependently selected to maintain the tetravalent nature of carbon,trivalent nature of nitrogen, the divalent nature of sulfur, and thedivalent nature of oxygen;

[0109] Q is optionally selected from formula (III):

[0110]  wherein D³, D⁴, J³, and J⁴ are independently selected from thegroup consisting of C, N, O, and S, no more than one of D³, D⁴, J³, andJ⁴ is O, no more than one of D³, D⁴, J³, and J⁴ is S, and no more thanthree of D¹, D², J¹, and J² are N with the proviso that R⁹, R¹⁰, R¹¹,and R¹² are each independently selected to maintain the tetravalentnature of carbon, trivalent nature of nitrogen, the divalent nature ofsulfur, and the divalent nature of oxygen;

[0111] Q is optionally selected from the group consisting of hydrido,alkyl, alkoxy, alkylamino, alkylthio, haloalkylthio, alkenyl, alkynyl,saturated heterocyclyl, partially saturated heterocyclyl, acyl, aroyl,heteroaroyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl,cycloalkenylalkyl, cycloalkylalkenyl, haloalkyl, haloalkoxy,haloalkenyl, halocycloalkyl, halocycloalkenyl, haloalkoxyalkyl,haloalkenyloxyalkyl, halocycloalkoxyalkyl, and halocycloalkenyloxyalkylwith the proviso that Z⁰ is selected from other than a single covalentbond when Q is hydrido;

[0112] K is (CR^(4a)R^(4b))_(n) wherein n is an integer selected from 1through 2;

[0113] R^(4a) and R^(4b) are independently selected from the groupconsisting of halo, hydrido, hydroxy, cyano, hydroxyalkyl, alkyl,alkenyl, alkoxyalkyl, aralkyl, heteroaralkyl, alkylthioalkyl, haloalkyl,haloalkenyl, and cyanoalkyl;

[0114] E⁰ is E¹, when K is (CR^(4a)R^(4b))_(n), wherein E¹ is selectedfrom the group consisting of a covalent single bond, O, S, C(O), C(S),C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R⁷), (R⁷)NC(S),OC(O)N(R⁷), (R⁷)NC(O)O, SC(S)N(R⁷), (R⁷)NC(S)S, SC(O)N(R⁷), (R⁷)NC(O)S,OC(S)N(R⁷), (R⁷)NC(S)O, N(R⁸)C(O)N(R⁷), (R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷),(R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂, S(O)₂N(R⁷)C(O),C(O)N(R⁷)S(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R⁷), ON(R⁷),CR^(4a)═CR^(4b), ethynylidene (C≡C; 1,2-ethynyl), and C═CR^(4a)R^(4b);

[0115] K is optionally (CH(R¹⁴))_(j)—T wherein j is selected from ainteger from 0 through 2 and T is selected from the group consisting ofsingle covalent bond, O, S, and N(R⁷) with the proviso that(CH(R¹⁴))_(j) is bonded to the uracil ring;

[0116] E⁰ is optionally E², when K is (CH(R¹⁴))_(j)—T, wherein E² isselected from the group consisting of a covalent single bond, C(O),C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R⁷),(R⁷)NC(S), (R⁷)NC(O)O, (R⁷)NC(S)S, (R⁷)NC(O)S, (R⁷)NC(S)O,N(R⁸)C(O)N(R⁷), (R⁷)NC(O)N(R⁸), N(R⁸)C(S)N(R⁷), (R⁷)NC(S)N(R⁸), S(O),S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂, S(O)₂N(H)C(O), C(O)N(H)S(O)₂, P(O)(R⁸),N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), and N(R⁷);

[0117] K is optionally G—(CH(R¹⁵))_(k) wherein k is selected from aninteger from 1 through 2 and G is selected from the group consisting ofO, S, and N(R⁷) with the proviso that R¹⁵ is other than hydroxy, cyano,halo, amino, alkylamino, dialkylamino, and sulfhydryl when k is 1;

[0118] E⁰ is optionally E³ when K is G—(CH(R¹⁵))_(k), wherein E³ isselected from the group consisting of a covalent single bond, O, S,C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R⁷), (R⁷)NC(O), C(S)N(R⁷),(R⁷)NC(S), OC(O)N(R⁷), (R⁷)NC(O)O, SC(S)N(R⁷), (R⁷)NC(S)S, SC(O)N(R⁷),(R⁷)NC(O)S, OC(S)N(R⁷), (R⁷)NC(S)O, N(R⁸)C(O)N(R⁷), (R⁷)NC(O)N(R⁸),N(R⁸)C(S)N(R⁷), (R⁷)NC(S)N(R⁸), S(O), S(O)₂, S(O)₂N(R⁷), N(R⁷)S(O)₂,P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R⁷), ON(R⁷), CR^(4a)═CR^(4b),ethynylidene (C≡C; 1,2-ethynyl), and C═CR^(4a)R^(4b);

[0119] Y⁰ is formula (IV):

[0120]  wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from thegroup consisting of C, N, O, S and a covalent bond with the provisosthat no more than one is a covalent bond, K² is independently selectedfrom the group consisting of C and N⁺, no more than one of D⁵, D⁶, J⁵,and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵, D⁶,J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶ are Oand S, no more than three of D⁵, D⁶, J⁵, and J⁶ is N when K² is N⁺, andno more than four of D⁵, D⁶, J⁵, and J⁶ are N when K² is carbon with theprovisos that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each independently selected tomaintain the tetravalent nature of carbon, trivalent nature of nitrogen,the divalent nature of sulfur, and the divalent nature of oxygen;

[0121] R¹⁶ and R¹⁷ are optionally independently taken together to form alinear moiety spacer having from 3 through 6 contiguous atoms connectedto form a ring selected from the group consisting of a cycloalkenyl ringhaving from 5 through 8 contiguous members, a partially saturatedheterocyclyl ring having from 5 through 8 contiguous members, aheteroaryl having from 5 through 6 contiguous members, and an aryl;

[0122] Q^(b) is selected from the group consisting of NR²⁰R²¹,⁺NR²⁰R²¹R²², oxy, alkyl, aminoalkylenyl, alkylamino, dialkylamino,dialkylsulfoniumalkyl, acylamino and Q^(be), wherein Q^(be) is hydridoand R²⁰, R²¹, and R²² are independently selected from the groupconsisting of hydrido, amino, alkyl, hydroxy, alkoxy,aminoalkylenyl,alkylamino, dialkylamino, and hydroxyalkyl with theprovisos that no more than one of R²⁰, R²¹, and R²² is hydroxy, alkoxy,alkylamino, amino, and dialkylamino at the same time and that R²⁰, R²¹,and R²² must be other than be hydroxy, alkoxy, alkylamino, amino, anddialkylamino when K² is N⁺;

[0123] R²⁰ and R²¹, R²⁰ and R²², and R²¹ and R²² are independentlyoptionally selected to form a spacer pair wherein a spacer pair is takentogether to form a linear moiety having from 4 through 7 contiguousatoms connecting the points of bonding of said spacer pair members toform a heterocyclyl ring having 5 through 8 contiguous members with theproviso that no more than one of the group consisting of spacer pairsR²⁰ and R²¹, R²⁰ and R²², and R²¹ and R²² is used at the same time;

[0124] Q^(b) is optionally selected from the group consisting ofN(R²⁶)SO₂N(R²³)(R²⁴), N(R²⁶)C(O)OR⁵, N(R²⁶)C(O)SR⁵, N(R²⁶)C(S)OR⁵ andN(R²⁶)C(S)SR⁵ with the proviso that no more than one of R²³, R²⁴, andR²⁶ is hydroxy, alkoxy, alkylamino, amino, and dialkylamino when two ofthe group consisting of R²³, R²⁴, and R²⁶ are bonded to the same atom;

[0125] Q^(b) is optionally selected from the group consisting ofdialkylsulfonium, trialkylphosphonium, C(NR²⁵)NR²³R²⁴,N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), N(R²⁶)C(O)N(R²³)(R²⁴), N(R²⁶)C(S)N(R²³)(R²⁴),C(NR²⁵)OR⁵, C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), C(S)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), ON(R²⁶)C(NR²⁵)N(R²³)(R²⁴),N(R²⁶)N(R²⁶)SO₂N(R²³)(R²⁴), C(NR²⁵)SR⁵, C(O)NR²³R²⁴, and C(O)NR²³R²⁴with the provisos that no more than one of R²³, R²⁴, and R²⁶ can behydroxy, alkoxy, alkylaminol, amino, or dialkylamino when two of thegroup consisting of R²³, R²⁴, and R²⁶ are bonded to the same atom andthat said Q^(b) group is bonded directly to a carbon atom;

[0126] R²³, R²⁴, R²⁵, and R²⁶ are independently selected from the groupconsisting of hydrido, alkyl, hydroxy, alkoxy, aminoalkylenyl,alkylamino, dialkylamino, amino, and hydroxyalkyl;

[0127] R²³ and R²⁴ are optionally taken together to form a linear spacermoiety having from 4 through 7 contiguous atoms connecting the points ofbonding to form a heterocyclyl ring having 5 through 8 contiguousmembers;

[0128] Q^(s) is selected from the group consisting of a single covalentbond, (CR³⁷R³⁸)_(b)—(W⁰)_(az) wherein az is an integer selected from 0through 1, b is an integer selected from 1 through 4, and W⁰ is selectedfrom the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S,C(S)S, C(O)N(R¹⁴), (R¹⁴)NC(O), C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴),SC(S)N(R¹⁴), SC(O)N(R¹⁴), OC(S)N(R¹⁴), N(R¹⁵)C(O)N(R¹⁴),(R¹⁴)NC(O)N(R¹⁵), N(R¹⁵)C(S)N(R¹⁴), (R¹⁴)NC(S)N(R¹⁵), S(O), S(O)₂,S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷),N(R¹⁴), ON(R¹⁴), (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d areintegers independently selected from 1 through 4, and W¹ is selectedfrom the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S,C(S)S, C(O)N(R¹⁴), (R¹⁴)NC(O), C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴),(R¹⁴)NC(O)O, SC(S)N(R¹⁴), (R¹⁴)NC(S)S, SC(O)N(R¹⁴), (R¹⁴)NC(O)S,OC(S)N(R¹⁴), (R¹⁴)NC(S)O, N(R¹⁵)C(O)N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵),N(R¹⁵)C(S)N(R¹⁴), (R¹⁴)NC(S)N(R¹⁵), S(O), S(O)₂, S(O)₂N(R¹⁴),N(R¹⁴)S(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R¹⁴), ON(R¹⁴),and (CH(R¹⁴))_(e)—W²²—(CH(R¹⁵))_(h) wherein e and h are integersindependently selected from 0 through 2 and W²² is selected from thegroup consisting of CR⁴¹═CR⁴², CR⁴¹R⁴²═C; vinylidene), ethynylidene(C≡C; 1,2-ethynyl), 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl,1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl,2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl,1,2-piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl, 2,6-piperazinyl,1,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,2,6-piperidinyl, 3,4-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl,2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, and3,4-tetrahydrofuranyl, with the provisos that R¹⁴ and R¹⁵ are selectedfrom other than halo and cyano when directly bonded to N and that(CR³⁷R³⁸)_(b), (CH(R¹⁴))_(c), (CH(R¹⁴))_(e) and are bonded to E⁰;

[0129] Y⁰ is optionally Q^(b)—Q^(ss) wherein Q^(ss) is selected from thegroup consisting of (CR³⁷R³⁸)_(f) wherein f is an integer selected from1 through 6, (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d are integersindependently selected from 1 through 4, and W¹ is selected from thegroup consisting of W¹ is selected from the group consisting of O, S,C(O), C(S), C(O)O, C(S)O, C(O)S, C(S)S, C(O)N(R¹⁴), (R¹⁴)NC(O),C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴), (R¹⁴)NC(O)O, SC(S)N(R¹⁴),(R¹⁴)NC(S)S, SC(O)N(R¹⁴), (R¹⁴)NC(O)S, OC(S)N(R¹⁴), (R¹⁴)NC(S)O,N(R¹⁵)C(O)N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵), N(R¹⁵)C(S)N(R¹⁴), (R¹⁴)NC(S)N(R¹⁵),S(O), S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸),P(O)(R⁸)N(R⁷), N(R¹⁴), ON(R¹⁴), and (CH(R¹⁴))_(e)—W²—(CH(R¹⁵))_(h)wherein e and h are integers independently selected from 0 through 2 andW² is selected from the group consisting of CR^(4a)═CR^(4b),ethynylidene (C≡C; 1,2-ethynyl), and C═CR^(4a)R^(4b) with the provisosthat R¹⁴ and R¹⁵ are selected from other than halo and cyano whendirectly bonded to N and that (CR³⁷R³⁸)_(f), (CH(R¹⁴))_(c), and(CH(R¹⁴))_(e) are bonded to E⁰;

[0130] Y⁰ is optionally Q^(b)—Q^(sss) wherein Q^(sss) is(CH(R³⁸))_(r)—W³, r is an integer selected from 1 through 3, W³ isselected from the group consisting of 1,1-cyclopropyl, 1,2-cyclopropyl,1,1-cyclobutyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl,1,4-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl,2,4-morpholinyl, 2,5-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl,3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl,2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl,1,3-piperidinyl, 1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl,3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2H-2,3-pyranyl,2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl, 4H-2,4-pyranyl,4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl, 2H-pyran-2-one-4,5-yl,4H-pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl,2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl,3,4-tetrahydropyranyl, and 3,5-tetrahydropyranyl, and each carbon andhyrido containing nitrogen member of the ring of the W³ other than thepoints of attachment is optionally substituted with one or more of thegroup consisting of R⁹, R¹⁰, R¹¹, and R¹², with the proviso that(CH(R³⁸))_(r) is bonded to E⁰ and Q^(b) is bonded to lowest numberedsubstituent position of each W³;

[0131] Y⁰ is optionally Q^(b)—Q^(sssr) wherein Q^(sssr) is(CH(R³⁸))_(r)—W⁴, r is an integer selected from 1 through 3, W⁴ isselected from the group consisting of 1,2-cyclobutyl, 1,2-cyclohexyl,1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl,2,3-morpholinyl, 2,4-morpholinyl, 2,5-morpholinyl, 2,6-morpholinyl,3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl,1,4-piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl,1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl, 2,3-piperidinyl,2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl,3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl,2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl,4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl,2H-pyran-2-one-4,5-yl, 4H-pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl,2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl,2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl,2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl, and 3,5-tetrahydropyranyl,and each carbon and hydrido containing nitrogen member of the ring ofthe W⁴ other than the points of attachment is optionally substitutedwith one or more of the group consisting of R⁹, R¹⁰, R¹¹, and R¹², withthe provisos that (CH(R³⁸))_(r) is bonded to E⁰ and Q^(b) is bonded tohighest number substituent position of each W⁴;

[0132] Y⁰ is optionally Q^(b)—Q^(ssss) wherein Q^(ssss) is(CH(R³⁸))_(r)—W⁵, r is an integer selected from 1 through 3, W⁵ isselected from the group consisting of 1,4-indenyl, 1,5-indenyl,1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl,2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl,2,4-benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl,3,4-benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,7-imidazo(1,2-a)pyridinyl,3,4-imidazo(1,2-a)pyridinyl, 3,5-imidazo(1,2-a)pyridinyl,3,6-imidazo(1,2-a)pyridinyl, 3,7-imidazo(1,2-a)pyridinyl, 2,4-indolyl,2,5-indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl,3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl,1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl,2,7-isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl,3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl,2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl,2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl,2,8-quinolinyl, 3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl,3,7-quinolinyl, 3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl,4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl,1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl,3,4-isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl,3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl,4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl, andeach carbon and hydrido containing nitrogen member of the ring of the W⁵other than the points of attachment is optionally substituted with oneor more of the group consisting of R⁹, R¹⁰, R¹¹, and R¹², with theproviso that Q^(b) is bonded to lowest number substituent position ofeach W⁵ and that (CH(R³⁸))_(r) is bonded to E⁰;

[0133] Y⁰ is optionally Q^(b)—Q^(ssssr) wherein Q^(ssssr) is(CH(R³⁸))_(r)—W⁶, r is an integer selected from 1 through 3, W⁶ isselected from the group consisting of 1,4-indenyl, 1,5-indenyl,1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl,2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl,2,4-benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl,3,4-benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,7-imidazo(1,2-a)pyridinyl,3,4-imidazo(1,2-a)pyridinyl, 3,5-imidazo(1,2-a)pyridinyl,3,6-imidazo(1,2-a)pyridinyl, 3,7-imidazo(1,2-a)pyridinyl, 2,4-indolyl,2,5-indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl,3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl,1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl,2,7-isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl,3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl,2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl,2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl,2,8-quinolinyl, 3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl,3,7-quinolinyl, 3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl,4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl,1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl,3,4-isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl,3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl,4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl, andeach carbon and hydrido containing nitrogen member of the ring of the W⁶other than the points of attachment is optionally substituted with oneor more of the group consisting of R⁹, R¹⁰, R¹¹, and R¹², with theproviso that Q^(b) is bonded to highest number substituent position ofeach W⁶ and that (CH(R³⁸))_(r) is bonded to E⁰.

[0134] In another embodiment of compounds of Formula I or apharmaceutically acceptable salt thereof,

[0135] J^(a) and J^(b) are independently selected from the groupconsisting of O and S;

[0136] B is formula (V):

[0137]  wherein D¹, D², J¹, J² and K¹ are independently selected fromthe group consisting of C, N, O, S and a covalent bond with the provisosthat no more than one is a covalent bond, no more than one of D¹, D²,J¹, J² and K¹ is O, no more than one of D¹, D², J¹, J² and K¹ is S, oneof D¹, D², J¹, J² and K¹ must be a covalent bond when two of D¹, D², J¹,J² and K¹ are O and S, and no more than four of D¹, D², J¹, J² and K¹are N;

[0138] R⁹, R¹⁰, R¹¹, R¹², R¹³, R¹⁶, R¹⁷, R¹⁸, R¹⁹, R³², R³³, R³⁴, R³⁵,and R³⁶ are independently selected from the group consisting of hydrido,acetamido, haloacetamido, amidino, guanidino, dialkylsulfonium,trialkylphosphonium, dialkylsulfoniumalkyl, carboxy, heteroaralkylthio,heteroaralkoxy, cycloalkylamino, acylalkyl, acylalkoxy, aryloylalkoxy,heterocyclyloxy, aralkylaryl, aralkyl, aralkenyl, aralkynyl,heterocyclyl, perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl,aralkylsulfinyl, aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl,cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl,cycloalkylsulfonylalkyl, heteroarylamino,N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, haloalkylthio,alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy,cycloalkoxy, cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy,cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy,halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl,hydroxy, amino, alkoxyamino, thio, nitro, lower alkylamino, alkylthio,alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl,heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl,arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl,heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl,haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido,alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, monoarylamidosulfonyl, arylsulfonamido,diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl,arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl,heterocyclylsulfonyl, heterocyclylthio, alkanoyl, alkenoyl, aroyl,heteroaroyl, aralkanoyl, heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl,alkynyl, alkenyloxy, alkenyloxyalky, alkylenedioxy, haloalkylenedioxy,cycloalkyl, cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl,lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy,hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, alkylenylamino,hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy,aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl,heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl,heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl,carboalkoxy, alkoxycarboxamido, alkylamidocarbonylamido,arylamidocarbonylamido, carboalkoxyalkyl, carboalkoxyalkenyl, carboxy,carboaralkoxy, carboxamido, carboxamidoalkyl, cyano, carbohaloalkoxy,phosphono, phosphonoalkyl, diaralkoxyphosphono, anddiaralkoxyphosphonoalkyl;

[0139] R¹⁶, R¹⁹, R³², R³³, R³⁴, R³⁵, and R³⁶ are independentlyoptionally Q^(b) with the proviso that no more than one of R¹⁶ and R¹⁹is Q^(b) at the same time and that Q^(b) is Q^(be);

[0140] B is optionally selected from the group consisting of hydrido,trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8alkynyl, C2-C8 haloalkyl, and C3-C8 haloalkenyl wherein each member ofgroup B is optionally substituted at any carbon up to and including 6atoms from the point of attachment of B to A with one or more of thegroup consisting of R³², R³³, R³⁴, R³⁵, and R³⁶;

[0141] B is optionally selected from the group consisting of C3-C12cycloalkyl, C5-C10 cycloalkenyl, and C4-C9 saturated heterocyclyl,wherein each ring carbon is optionally substituted with R³³, a ringcarbon other than the ring carbon at the point of attachment of B to Ais optionally substituted with oxo provided that no more than one ringcarbon is substituted by oxo at the same time, ring carbons and anitrogen adjacent to the carbon atom at the point of attachment areoptionally substituted with R⁹ or R¹³, a ring carbon or nitrogenadjacent to the R⁹ position and two atoms from the point of attachmentis optionally substituted with R¹⁰, a ring carbon or nitrogen adjacentto the R¹³ position and two atoms from the point of attachment isoptionally substituted with R¹², a ring carbon or nitrogen three atomsfrom the point of attachment and adjacent to the R¹⁰ position isoptionally substituted with R¹¹, a ring carbon or nitrogen three atomsfrom the point of attachment and adjacent to the R¹² position isoptionally substituted with R³³, and a ring carbon or nitrogen fouratoms from the point of attachment and adjacent to the R¹¹ and R³³positions is optionally substituted with R³⁴;

[0142] A is selected from the group consisting of single covalent bond,(W⁷)_(rr)—(CH(R¹⁵))_(pa) and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is aninteger selected from 0 through 1, pa is an integer selected from 0through 6, and W⁷ is selected from the group consisting of O, S, C(O),C(O)N(R⁷), C(S)N(R⁷), (R⁷)NC(O), (R⁷)NC(S), and N(R⁷) with the provisothat no more than one of the group consisting of rr and pa can be 0 atthe same time;

[0143] R⁷ and R⁸ are independently selected from the group consisting ofhydrido, hydroxy, alkyl, and alkoxyalkyl;

[0144] R¹⁴, R¹⁵, R³⁷, and R³⁸ are independently selected from the groupconsisting of hydrido, hydroxy, halo, alkyl, alkoxyalkyl, haloalkyl,haloalkoxy, and haloalkoxyalkyl;

[0145] R¹⁴ and R³⁸ can be independently selected from the groupconsisting of aroyl and heteroaroyl;

[0146] Ψ is selected from the group consisting of NR⁵, C(O), and S(O)₂;

[0147] R⁵ is selected from the group consisting of hydrido, hydroxy,alkyl, and alkoxy;

[0148] R³⁹ and R⁴⁰ are independently selected from the group consistingof hydrido, hydroxy, halo, hydroxyalkyl, alkyl, alkoxyalkyl, haloalkyl,haloalkoxy, and haloalkoxyalkyl;

[0149] M is selected from the group consisting of N and R¹—C;

[0150] R¹ is selected from the group consisting of hydrido, alkyl,alkenyl, cyano, halo, haloalkyl, haloalkoxy, haloalkylthio, amino,aminoalkyl, alkylamino, amidino, guanidino, hydroxy, hydroxyamino,alkoxy, hydroxyalkyl, alkoxyamino, thiol, alkylthio, and phosphono;

[0151] R² is Z⁰—Q;

[0152] Z⁰ is selected from the group consisting of covalent single bond,(CR⁴¹R⁴²)_(q) wherein q is an integer selected from 1 through 3,(CH(R⁴¹))_(g)—W⁰—(CH(R⁴²))_(p) wherein g and p are integersindependently selected from 0 through 3 and W⁰ is selected from thegroup consisting of O, S, C(O), S(O), S(O)₂, N(R⁴¹), and ON(R⁴¹), and(CH(R⁴¹))_(e)—W²²—(CH(R⁴²))_(h) wherein e and h are integersindependently selected from 0 through 2 and W²² is selected from thegroup consisting of CR⁴¹═CR⁴², 1,2-cyclopropyl, 1,2-cyclobutyl,1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl,2,3-morpholinyl, 2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl,3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl,2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl,2,4-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 1,2-pyrrolidinyl,1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl,3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, with the proviso thatZ⁰ is directly bonded to the uracil ring;

[0153] R⁴¹ and R⁴² are independently selected from the group consistingof amidino, hydroxyamino, hydrido, hydroxy, amino, and alkyl;

[0154] Q is selected from the group consisting of hydrido, with theproviso that Z⁰ is other than a covalent single bond, the formula (II):

[0155] wherein D¹, D², J¹, J² and K¹ are independently selected from thegroup consisting of C, N, O, S and a covalent bond with the provisosthat no more than one is a covalent bond, no more than one of D¹, D²,J¹, J² and K¹ is O, no more than one of D¹, D², J¹, J² and K¹ is S, oneof D¹, D², J¹, J² and K¹ must be a covalent bond when two of D¹, D², J¹,J² and K¹ are O and S, and no more than four of D¹, D², J¹, J² and K¹ isN, with the proviso that R⁹, R¹⁰, R¹¹, R¹², and R¹³ are eachindependently selected to maintain the tetravalent nature of carbon,trivalent nature of nitrogen, the divalent nature of sulfur, and thedivalent nature of oxygen;

[0156] K is (CR^(4a)R^(4b))_(n) wherein n is an integer selected from 1through 2;

[0157] R^(4a) and R^(4b) are independently selected from the groupconsisting of halo, hydrido, hydroxyalkyl, alkyl, alkoxyalkyl,alkylthioalkyl, and haloalkyl;

[0158] E⁰ is selected from the group consisting of a covalent singlebond, C(O), C(S), C(O)N(R⁷), (R⁷)NC(O), S(O)₂, (R⁷)NS(O)₂, andS(O)₂N(R⁷);

[0159] Y⁰ is formula (IV):

[0160]  wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from thegroup consisting of C, N, O, S and a covalent bond with the provisosthat no more than one is a covalent bond, K² is C, no more than one ofD⁵, D⁶, J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S,one of D⁵, D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶,J⁵, and J⁶ are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ areN when K² is carbon with the provisos that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ areeach independently selected to maintain the tetravalent nature ofcarbon, trivalent nature of nitrogen, the divalent nature of sulfur, andthe divalent nature of oxygen;

[0161] Q^(b) is selected from the group consisting of NR²⁰R²¹,⁺NR²⁰R²¹R²², aminoalkylenyl, and Q^(be), wherein Q^(be) is hydrido andR²⁰, R²¹, and R²² are independently selected from the group consistingof hydrido, alkyl, hydroxy, amino, aminoalkylenyl, dialkylamino,alkylamino, and hydroxyalkyl with the proviso that no more than one ofR²⁰ and R²¹ is hydroxy, amino, alkylamino, or dialkylamino at the sametime;

[0162] Q^(b) is optionally selected from the group consisting ofC(NR²⁵)NR²³R²⁴, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), C(O)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),N(R²⁶)N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and ON(R²⁶)C(NR²⁵)N(R²³)(R²⁴) with theprovisos that no more than one of R²³, R²⁴, and R²⁶ is hydroxy,alkylamino, amino, or dialkylamino when two of the group consisting ofR²³, R²⁴, and R²⁶ are bonded to the same atom;

[0163] R²³, R²⁴, R²⁵, and R²⁶ are independently selected from the groupconsisting of hydrido, alkyl, hydroxy, amino, alkylenylamino,dialkylamino, alkylamino, and hydroxyalkyl;

[0164] Q^(s) is selected from the group consisting of a single covalentbond, (CR³⁷R³⁸)_(b)—(W⁰)_(az) wherein az is an integer selected from 0through 1, b is an integer selected from 1 through 5, and W⁰ is selectedfrom the group consisting of O, C(O), S(O), S(O)₂, S(O)₂N(R¹⁴),N(R¹⁴)S(O)₂, and N(R¹⁴), (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and dare integers independently selected from 1 through 4 and W¹ is selectedfrom the group consisting of O, S, C(O), C(S), C(O)O, C(S)O, C(O)S,C(S)S, C(O)N(R¹⁴), (R¹⁴)NC(O), C(S)N(R¹⁴), (R¹⁴)NC(S), OC(O)N(R¹⁴),(R¹⁴)NC(O)O, SC(S)N(R¹⁴), (R¹⁴)NC(S)S, SC(O)N(R¹⁴), (R¹⁴)NC(O)S,OC(S)N(R¹⁴), (R¹⁴)NC(S)O, N(R¹⁵)C(O)N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵),N(R¹⁵)C(S)N(R¹⁴), (R¹⁴)NC(S)N(R¹⁵), S(O), S(O)₂, S(O)₂N(R¹⁴),N(R¹⁴)S(O)₂, P(O)(R⁸), N(R⁷)P(O)(R⁸), P(O)(R⁸)N(R⁷), N(R¹⁴), ON(R¹⁴),and (CH(R¹⁴))_(e)—W²²—(CH(R¹⁵))_(h) wherein e and h are integersindependently selected from 0 through 2 and W²² is selected from thegroup consisting of CR⁴¹═CR⁴², CR⁴¹R⁴²═C; vinylidene), ethynylidene(C≡C; 1,2-ethynyl), 1,2-cyclopropyl, 1,2-cyclobutyl, 1,2-cyclohexyl,1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl,2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5-morpholinyl,1,2-piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl, 2,6-piperazinyl,1,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,2,6-piperidinyl, 3,4-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl,2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, and3,4-tetrahydrofuranyl, with the provisos that R¹⁴ and R¹⁵ are selectedfrom other than halo and cyano when directly bonded to N and that(CR³⁷R³⁸)_(b), (CH(R¹⁴))_(c), and (CH(R¹⁴))_(e) are bonded to E⁰;

[0165] Y⁰ is optionally Q^(b)—Q^(SS) wherein Q^(ss) is selected from thegroup consisting of (CR³⁷R³⁸)_(f) wherein f is an integer selected from1 through 4, (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d are integersindependently selected from 1 through 2, and W¹ is selected from thegroup consisting of W¹ is selected from the group consisting of O, S,C(O), C(O)N(R¹⁴), (R¹⁴)NC(O), N(R¹⁵)C(O)N(R¹⁴), (R¹⁴)NC(O)N(R¹⁵),N(R¹⁴), ON(R¹⁴), and (CH(R¹⁴))_(e)—W²—(CH(R¹⁵))_(h) wherein e and h areintegers independently selected from 0 through 2 and W² is selected fromthe group consisting of CR^(4a)═CR^(4b),ethynylidene (C≡C; 1,2-ethynyl),and C═CR^(4a)R^(4b) with the provisos that R¹⁴ and R¹⁵ are selected fromother than halo when directly bonded to N and that (CR³⁷R³⁸)_(f),(CH(R¹⁴))_(c), and (CH(R¹⁴))_(e) are bonded to E⁰;

[0166] Y⁰ is optionally Q^(b)—Q^(sss) wherein Q^(sss) is(CH(R³⁸))_(r)—W³, r is an integer selected from 1 through 2, W³ isselected from the group consisting of 1,1-cyclopropyl, 1,2-cyclopropyl,1,1-cyclobutyl, 1,2-cyclobutyl, 1,2-cyclohexyl, 1,3-cyclohexyl,1,4-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl, 2,3-morpholinyl,2,4-morpholinyl, 2,5-morpholinyl, 2,6morpholinyl, 3,4-morpholinyl,3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 1,4-piperazinyl,2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl, 1,2-piperidinyl,1,3-piperidinyl, 1,4-piperidinyl, 2,3-piperidinyl, 2,4-piperidinyl,2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 3,5-piperidinyl,3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl, 2,3-pyrrolidinyl,2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl, 2H-2,3-pyranyl,2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl. 4H-2,4pyranyl,4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl, 2H-pyran-2-one-4,5-yl,4H-pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl, 2,3-tetrahydropyranyl,2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl, 2,6-tetrahydropyranyl,3,4-tetrahydropyranyl, and 3,5-tetrahydropyranyl, and each carbon andhyrido containing nitrogen member of the ring of the W³ other than thepoints of attachment is optionally substituted with one or more of thegroup consisting of R⁹, R¹⁰, R¹¹, and R¹², with the proviso that(CH(R³⁸))_(r) is bonded to E⁰ and Q^(b) is bonded to lowest numberedsubstituent position of each W³;

[0167] Y⁰ is optionally Q^(b)—Q^(sssr) wherein Q^(sssr) is(CH(R³⁸))_(r)—W⁴, r is an integer selected from 1 through 2, W⁴ isselected from the group consisting of 1,2-cyclobutyl, 1,2-cyclohexyl,1,3-cyclohexyl, 1,4-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl,2,3-morpholinyl, 2,4-morpholinyl, 2,5-morpholinyl, 2,6-morpholinyl,3,4-morpholinyl, 3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl,1,4-piperazinyl, 2,3-piperazinyl, 2,5-piperazinyl, 2,6-piperazinyl,1,2-piperidinyl, 1,3-piperidinyl, 1,4-piperidinyl, 2,3-piperidinyl,2,4-piperidinyl, 2,5-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl,3,5-piperidinyl, 3,6-piperidinyl, 1,2-pyrrolidinyl, 1,3-pyrrolidinyl,2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl, 3,4-pyrrolidinyl,2H-2,3-pyranyl, 2H-2,4-pyranyl, 2H-2,5-pyranyl, 4H-2,3-pyranyl,4H-2,4-pyranyl, 4H-2,5-pyranyl, 2H-pyran-2-one-3,4-yl,2H-pyran-2-one4,5-yl, 4H-pyran-4-one-2,3-yl, 2,3-tetrahydrofuranyl,2,4-tetrahydrofuranyl, 2,5-tetrahydrofuranyl, 3,4-tetrahydrofuranyl,2,3-tetrahydropyranyl, 2,4-tetrahydropyranyl, 2,5-tetrahydropyranyl,2,6-tetrahydropyranyl, 3,4-tetrahydropyranyl, and 3,5-tetrahydropyranyl,and each carbon and hyrido containing nitrogen member of the ring of theW⁴ other than the points of attachment is optionally substituted withone or more of the group consisting of R⁹, R¹⁰, R¹¹, and R¹², with theprovisos that (CH(R³⁸))_(r) is bonded to E⁰ and Q^(b) is bonded tohighest number substituent position of each W⁴;

[0168] Y⁰ optionally Q^(b)—Q^(ssss) wherein Q^(sss) is (CH(R³⁸))_(r)—W⁵,r is an integer selected from 1 through 2, W⁵ is selected from the groupconsisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl,2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl,3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4-benzofuranyl,2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,7-imidazo(1,2-a)pyridinyl,3,4-imidazo(1,2-a)pyridinyl, 3,5-imidazo(1,2-a)pyridinyl,3,6-imidazo(1,2-a)pyridinyl, 3,7-imidazo(1,2-a)pyridinyl, 2,4-indolyl,2,5-indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl,3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl,1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl,2,7-isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl,3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl,2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl,2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl,2,8-quinolinyl, 3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl,3,7-quinolinyl, 3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl,4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl,1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl,3,4-isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl,3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl,4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl, andeach carbon and hyrido containing nitrogen member of the ring of the W⁵other than the points of attachment is optionally substituted with oneor more of the group consisting of R⁹, R¹⁰, R¹¹, and R¹², with theproviso that Q^(b) is bonded to lowest number substituent position ofeach W⁵ and that (CH(R³⁸))_(r) is bonded to E⁰;

[0169] Y⁰ is optionally Q^(b)—Q^(ssssr) wherein Q^(ssssr) is(CH(R³⁸))_(r)—W⁶, r is an integer selected from 1 through 2, W⁶ isselected from the group consisting of 1,4-indenyl, 1,5-indenyl,1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl, 2,5-indenyl,2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl, 3,7-indenyl,2,4-benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl,3,4-benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,7-imidazo(1,2-a)pyridinyl,3,4-imidazo(1,2-a)pyridinyl, 3,5-imidazo(1,2-a)pyridinyl,3,6-imidazo(1,2-a)pyridinyl, 3,7-imidazo(1,2-a)pyridinyl, 2,4-indolyl,2,5-indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl,3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5isoindolyl, 1,6-isoindolyl,2,4-isoindolyl, 2,5isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl,1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl,3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl,2,7-benzoxazolyl, 3,4-benzisoxazolyl, 3,5-benzisoxazolyl,3,6-benzisoxazolyl, 3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl,1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl,2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl,2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl,3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl,3,8-quinolinyl, 4,5-quinotinyl, 4,6-quinolinyl, 4,7-quinolinyl,4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5-cinnolinyl,3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl,4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl, and each carbon andhyrido containing nitrogen member of the ring of the W⁶ other than thepoints of attachment is optionally substituted with one or more of thegroup consisting of R⁹, R¹⁰, R¹¹, and R¹², with the proviso that Q^(b)is bonded to highest number substituent position of each W⁶ and that(CH(R³⁸))_(r) is bonded to E⁰.

[0170] In a preferred embodiment of compounds of Formula I or apharmaceutically acceptable salt thereof,

[0171] J^(a) and J^(b) are each O;

[0172] B is formula (V):

[0173]  wherein D¹, D², J¹, J² and K¹ are independently selected fromthe group consisting of C, N, O, S and a covalent bond with the provisosthat no more than one is a covalent bond, no more than one of D¹, D²,J¹, J² and K¹ is O, no more than one of D¹, D², J¹, J² and K¹ is S, oneof D¹, D², J¹, J² and K¹ must be a covalent bond when two of D¹, D², J¹,J² and K¹ are O and S, and no more than four of D¹,D², J¹, J² and K¹ areN;

[0174] R⁹, R¹⁰, R¹¹, R¹², R¹³, R³², R³³, R³⁴, R³⁵, and R³⁶ areindependently selected from the group consisting of hydrido, acetamido,haloacetamido, amidino ,guanidino, alkylenedioxy, haloalkylthio,alkanoyloxy, alkoxy, alkoxyalkyl, haloalkoxylalkyl, hydroxy, amino,alkoxyamino, nitro, lower alkylamino, alkylthio, alkylthioalkyl,alkylsulfinyl, alkylsulfonyl, alkylsulfonylalkyl, aryl, aralkyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido,alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, alkanoyl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl,haloalkenyl, haloalkoxy, hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl,haloalkoxyalkyl, carboxyalkyl, carboalkoxy, carboxy, carboxamido,carboxamidoalkyl, and cyano;

[0175] R¹⁶, R¹⁹, R³², R³³, R³⁴, R³⁵, and R³⁶ are independentlyoptionally Q^(b) with the proviso that no more than one of R¹⁶ and R¹⁹is Q^(b) at the same time and that Q^(b) is Q^(be);

[0176] B is optionally selected from the group consisting of hydrido,trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8alkynyl, and C2-C8 haloalkyl, wherein each member of group B isoptionally substituted at any carbon up to and including 6 atoms fromthe point of attachment of B to A with one or more of the groupconsisting of R³², R³³, R³⁴, R³⁵, and R³⁶;

[0177] B is optionally selected from the group consisting of C3-C12cycloalkyl and C4-C9 saturated heterocyclyl, wherein each ring carbonmay be optionally substituted with R³³, a ring carbon other than thering carbon at the point of attachment of B to A is optionallysubstituted with oxo provided that no more than one ring carbon issubstituted by oxo at the same time, ring carbons and a nitrogenadjacent to the carbon atom at the point of attachment may be optionallysubstituted with R⁹ or R¹³, a ring carbon or nitrogen adjacent to the R⁹position and two atoms from the point of attachment is optionallysubstituted with R¹⁰, a ring carbon or nitrogen adjacent to the R¹³position and two atoms from the point of attachment is optionallysubstituted with R¹², a ring carbon or nitrogen three atoms from thepoint of attachment and adjacent to the R¹⁰ position is optionallysubstituted with R¹¹, a ring carbon or nitrogen three atoms from thepoint of attachment and adjacent to the R¹² position is optionallysubstituted with R³³, and a ring carbon or nitrogen four atoms from thepoint of attachment and adjacent to the R¹¹ and R³³ positions isoptionally substituted with R³⁴;

[0178] A is selected from the group consisting of single covalent bond,(W⁷)_(rr)—(CH(R¹⁵))_(pa) and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is aninteger selected from 0 through 1, pa is an integer selected from 0through 6, and W⁷ is selected from the group consisting of O, S, C(O),(R⁷)NC(O), (R⁷)NC(S), and N(R⁷) with the proviso that no more than oneof the group consisting of rr and pa is 0 at the same time;

[0179] R⁷ is selected from the group consisting of hydrido, hydroxy, andalkyl;

[0180] R¹⁵ is selected from the group consisting of hydrido, hydroxy,halo, alkyl, and haloalkyl;

[0181] Ψ is selected from the group consisting of NH and NOH;

[0182] M is selected from the group consisting of N and R¹—C;

[0183] R¹ is selected from the group consisting of hydrido, alkyl,alkenyl, cyano, halo, haloalkyl, haloalkoxy, haloalkylthio, amino,aminoalkyl, alkylamino, amidino, hydroxy, hydroxyamino, alkoxy,hydroxyalkyl, alkoxyamino, thiol, and alkylthio;

[0184] R² is Z⁰—Q;

[0185] Z⁰ is selected from the group consisting of covalent single bond,(CR⁴¹R⁴²)_(q) wherein q is an integer selected from 1 through 3,(CH(R⁴¹))_(g)—W⁰—(CH(R⁴²))_(p) wherein g and p are integersindependently selected from 0 through 3 and W⁰ is selected from thegroup consisting of O, S, C(O), S(O), N(R⁴¹), and ON(R⁴¹), and(CH(R⁴¹))_(e)—W²²—(CH(R⁴²))_(h) wherein e and h are integersindependently selected from 0 through 1 and W²² is selected from thegroup consisting of CR⁴¹═CR⁴², 1,2-cyclopropyl, 1,2-cyclobutyl,1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl,2,3-morpholinyl, 2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl,3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl,2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl,2,4-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 1,2-pyrrolidinyl,1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl,3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, with the proviso thatZ⁰ is directly bonded to the uracil ring;

[0186] R⁴¹ and R⁴² are independently selected from the group consistingof amidino, hydroxyamino, hydrido, hydroxy, amino, and alkyl;

[0187] Q is selected from the group consisting of hydrido, with theproviso that Z⁰ is other than a covalent single bond, and the formula(II):

[0188]  wherein D¹, D², J¹, J² and K¹ are independently selected fromthe group consisting of C, N, O, S and a covalent bond with the provisosthat no more than one is a covalent bond, no more than one of D¹, D²,J¹, J² and K¹ is O, no more than one of D¹, D², J¹, J² and K¹ is S, oneof D¹, D², J¹, J² and K¹ must be a covalent bond when two of D¹, D², J¹,J² and K¹ are O and S, and no more than four of D¹, D², J¹, J² and K¹are N, with the proviso that R⁹, R¹⁰, R¹¹, R¹², and R¹³ are eachindependently selected to maintain the tetravalent nature of carbon,trivalent nature of nitrogen, the divalent nature of sulfur, and thedivalent nature of oxygen;

[0189] K is (CR^(4a)R^(4b))_(n) wherein n is an integer selected from 1through 2;

[0190] R^(4a) and R^(4b) are independently selected from the groupconsisting of halo, hydrido, hydroxyalkyl, alkyl, alkoxyalkyl,alkylthioalkyl, and haloalkyl;

[0191] E⁰ is E¹, when K is (CR^(4a)R^(4b))_(n), wherein E¹ is selectedfrom the group consisting of a covalent single bond, C(O), C(S),C(O)N(R⁷), (R⁷)NC(O), S(O)₂, (R⁷)NS(O)₂, and S(O)₂N(R⁷);

[0192] Y⁰ is formula (IV):

[0193]  wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from thegroup consisting of C, N, O, S and a covalent bond with the provisosthat no more than one is a covalent bond, K² is C, no more than one ofD⁵, D⁶, J⁵, and J⁶ is O, no more than one of D⁵,D⁶, J⁵,and J⁶ is S, oneof D⁵, D⁶, J⁵,and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, andJ⁶ are O and S, and no more than four of D⁵, D⁶, J⁵ and J⁶ are N withthe proviso that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each independently selectedto maintain the tetravalent nature of carbon, trivalent nature ofnitrogen, the divalent nature of sulfur, and the divalent nature ofoxygen;

[0194] R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,alkoxy, hydroxy, amino, nitro, alkoxyamino, lower alkylamino, alkylthio,alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, alkenyl,halo, haloalkyl, haloalkoxy, hydroxyalkyl, alkylenylamino,haloalkoxyalkyl, carboalkoxy, and cyano;

[0195] Q^(b) is selected from the group consisting of NR²⁰R²¹,aminoalkylenyl, Q^(be) wherein Q^(be) is hydrido,N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the provisos that nomore than one of R²⁰ and R²¹ is hydroxy, amino, alkylamino, ordialkylamino at the same time and that no more than one of R²³ and R²⁴is hydroxy, amino, alkylamino, or dialkylamino at the same time;

[0196] R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected fromthe group consisting of hydrido, alkyl, hydroxy, aminoalkylenyl, amino,dialkylamino, alkylamino, and hydroxyalkyl;

[0197] Q^(s) is selected from the group consisting of a single covalentbond, (CR³⁷R³⁸)_(b) wherein b is an integer selected from 1 through 4,and (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d are integersindependently selected from 1 through 3 and W¹ is selected from thegroup consisting of C(O)N(R¹⁴), (R¹⁴)NC(O), S(O), S(O)₂, S(O)₂N(R¹⁴),N(R¹⁴)S(O)₂, and N(R¹⁴), with the provisos that R¹⁴ is selected fromother than halo when directly bonded to N and that (CR³⁷R³⁸)_(b), and(CH(R¹⁴))_(c) are bonded to E⁰;

[0198] R¹⁴ is selected from the group consisting of hydrido, halo,alkyl, and haloalkyl;

[0199] R³⁷ and R³⁸ are independently selected from the group consistingof hydrido, alkyl, and haloalkyl;

[0200] R³⁸ is optionally selected from the group consisting of aroyl andheteroaroyl;

[0201] Y⁰ is optionally Q^(b)—Q^(ss) wherein Q^(ss) is(CH(R¹⁴))_(e)—W²—(CH(R¹⁵))_(h), wherein e and h are integersindependently selected from 1 through 2 and W² is CR^(4a)═CR^(4b) withthe proviso that (CH(R¹⁴))_(e) is bonded to E⁰;

[0202] Y⁰ is optionally selected from the group consisting ofQ^(b)—Q^(ssss) and Q^(b)—Q^(ssssr) wherein Q^(ssss) is (CH(R³⁸))_(r)—W⁵and Q^(ssssr) is (CH(R³⁸))_(r)—W⁶, r is an integer selected from 1through 2, and W⁵ and W⁶ are independently selected from the groupconsisting of 1,4-indenyl, 1,5-indenyl, 1,6-indenyl, 1,7-indenyl,2,7-indenyl, 2,6-indenyl, 2,5-indenyl, 2,4-indenyl, 3,4-indenyl,3,5-indenyl, 3,6-indenyl, 3,7-indenyl, 2,4benzofuranyl,2,5-benzofuranyl, 2,6-benzofuranyl, 2,7-benzofuranyl, 3,4-benzofuranyl,3,5-benzofuranyl, 3,6-benzofuranyl, 3,7-benzofuranyl,2,4-benzothiophenyl, 2,5-benzothiophenyl, 2,6-benzothiophenyl,2,7-benzothiophenyl, 3,4-benzothiophenyl, 3,5-benzothiophenyl,3,6-benzothiophenyl, 3,7-benzothiophenyl, 2,7-imidazo(1,2-a)pyridinyl,3,4-imidazo(1,2-a)pyridinyl, 3,5-imidazo(1,2-a)pyridinyl,3,6-imidazo(1,2-a)pyridinyl, 3,7-imidazo(1 ,2-a)pyridinyl, 2,4-indolyl,2,5-indolyl, 2,6-indolyl, 2,7-indolyl, 3,4-indolyl, 3,5-indolyl,3,6-indolyl, 3,7-indolyl, 1,4-isoindolyl, 1,5-isoindolyl,1,6-isoindolyl, 2,4-isoindolyl, 2,5-isoindolyl, 2,6-isoindolyl,2,7-isoindolyl, 1,3-isoindolyl, 3,4-indazolyl, 3,5-indazolyl,3,6-indazolyl, 3,7-indazolyl, 2,4-benzoxazolyl, 2,5-benzoxazolyl,2,6-benzoxazolyl, 2,7-benzoxazolyl, 3,4-benzisoxazolyl,3,5-benzisoxazolyl, 3,6-benzisoxazolyl, 3,7-benzisoxazolyl,1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl, 1,7-naphthyl, 1,8-naphthyl,2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl, 2,7-naphthyl, 2,8-naphthyl,2,4-quinolinyl, 2,5-quinolinyl, 2,6-quinolinyl, 2,7-quinolinyl,2,8-quinolinyl, 3,4-quinolinyl, 3,5-quinolinyl, 3,6-quinolinyl,3,7-quinolinyl, 3,8-quinolinyl, 4,5-quinolinyl, 4,6-quinolinyl,4,7-quinolinyl, 4,8-quinolinyl, 1,4-isoquinolinyl, 1,5-isoquinolinyl,1,6-isoquinolinyl, 1,7-isoquinolinyl, 1,8-isoquinolinyl,3,4-isoquinolinyl, 3,5-isoquinolinyl, 3,6-isoquinolinyl,3,7-isoquinolinyl, 3,8-isoquinolinyl, 4,5-isoquinolinyl,4,6-isoquinolinyl, 4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl,3,5-cinnolinyl, 3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl,4,5-cinnolinyl, 4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl, andeach carbon and hyrido containing nitrogen member of the ring of the W⁵and of the ring of the W⁶, other than the points of attachment of W⁵ andW⁶, is optionally substituted with one or more of the group consistingof R⁹, R¹⁰, R¹¹, and R¹², with the provisos that Q^(b) is bonded tolowest number substituent position of each W⁵, Q^(b) is bonded tohighest number substituent position of each W⁶, and (CH(R³⁸))_(r) isbonded to E⁰.

[0203] In a more preferred embodiment of compounds of Formula I or apharmaceutically acceptable salt thereof,

[0204] J^(a) and J^(b) are each O;

[0205] B is selected from the group consisting of aryl and heteroarylwherein a carbon adjacent to the carbon at the point of attachment isoptionally substituted by R³², the other carbon adjacent to the carbonat the point of attachment is optionally substituted by R³⁶, a carbonadjacent to R³² and two atoms from the carbon at the point of attachmentis optionally substituted by R³³, a carbon adjacent to R³⁶ and two atomsfrom the carbon at the point of attachment is optionally substituted byR³⁵, and any carbon adjacent to both R³³ and R³⁵ is optionallysubstituted by R³⁴;

[0206] R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from thegroup consisting of hydrido, acetamido, haloacetamido, amidino,guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy, hydroxy,amino, alkoxyamino, alkanoyl, haloalkanoyl, nitro, lower alkylamino,alkylthio, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heteroaryl,heterocyclyl, alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl,dialkyl amidosulfonyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl,haloalkoxy, hydroxyalkyl, alkylenylamino, carboalkoxy, carboxy,carboxamido, cyano, and Q^(b);

[0207] B is optionally selected from the group consisting of hydrido,trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8alkynyl, and C2-C8 haloalkyl, wherein each member of group B isoptionally substituted at any carbon up to and including 6 atoms fromthe point of attachment of B to A with one or more of the groupconsisting of R³², R³³, R³⁴, R³⁵, and R³⁶;

[0208] B is optionally selected from the group consisting of C3-C12cycloalkyl and C4-C9 saturated heterocyclyl, wherein each ring carbon isoptionally optionally substituted with R³³, a ring carbon other than thering carbon at the point of attachment of B to A is optionallysubstituted with oxo provided that no more than one ring carbon issubstituted by oxo at the same time, ring carbons and a nitrogenadjacent to the carbon atom at the point of attachment are optionallysubstituted with R⁹ or R¹³, a ring carbon or nitrogen adjacent to the R⁹position and two atoms from the point of attachment is optionallysubstituted with R¹⁰, a ring carbon or nitrogen adjacent to the R¹³position and two atoms from the point of attachment is optionallysubstituted with R¹², a ring carbon or nitrogen three atoms from thepoint of attachment and adjacent to the R¹⁰ position is optionallysubstituted with R¹¹, a ring carbon or nitrogen three atoms from thepoint of attachment and adjacent to the R¹² position is optionallysubstituted with R³³, and a ring carbon or nitrogen four atoms from thepoint of attachment and adjacent to the R¹¹ and R³³ positions isoptionally substituted with R³⁴;

[0209] R⁹, R¹⁰, R¹¹, R¹², and R¹³ are independently selected from thegroup consisting of hydrido, acetamido, haloacetamido, alkoxyamino,alkanoyl, haloalkanoyl, amidino, guanidino, alkylenedioxy,haloalkylthio, alkoxy, hydroxy, amino, lower alkylamino, alkylthio,alkylsulfinyl, alkylsulfonyl, alkylsulfonamido, amidosulfonyl, monoalkylamidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, aminoalkyl, carboalkoxy, carboxyalkyl,carboxy, carboxamido, and cyano;

[0210] A is selected from the group consisting of single covalent bondand (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected from 0through 1, pa is an integer selected from 0 through 3, and W⁷ isselected from the group consisting of O, S, C(O), (R⁷)NC(O), (R⁷)NC(S),and N(R⁷);

[0211] R⁷ is selected from the group consisting of hydrido, hydroxy andalkyl;

[0212] R¹⁵ is selected from the group consisting of hydrido, hydroxy,halo, alkyl, and haloalkyl;

[0213] Ψ is NH;

[0214] M is selected from the group consisting of N and R¹—C;

[0215] R¹ is selected from the group consisting of hydrido, alkyl,cyano, halo, haloalkyl, haloalkoxy, amino, aminoalkyl, alkylamino,amidino, hydroxy, hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino,thiol, and alkylthio;

[0216] R² is Z⁰—Q;

[0217] Z⁰ is selected from the group consisting of covalent single bondand (CR⁴¹R⁴²)_(q) wherein q is an integer selected from 1 through 2,(CH(R⁴¹))_(g)—W⁰—(CH(R⁴²))_(p) wherein g and p are integersindependently selected from 0 through 3 and W⁰ is selected from thegroup consisting of O, S, and N(R⁴¹), and(CH(R⁴¹))_(e)—W²²—(CH(R⁴²))_(h) wherein e and h are integersindependently selected from 0 through 1 and W²² is selected from thegroup consisting of CR⁴¹═CR⁴², 1,2-cyclopropyl, 1,2-cyclobutyl,1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl,2,3-morpholinyl, 2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl,3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl,2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl,2,4-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 1,2-pyrrolidinyl,1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl,3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, with the proviso thatZ⁰ is directly bonded to the uracil ring;

[0218] R⁴¹ and R⁴² are independently selected from the group consistingof hydrido, hydroxy, and amino;

[0219] Q is selected from the group consisting of hydrido, with theproviso that Z⁰ is other than a covalent single bond, aryl, andheteroaryl, wherein a carbon adjacent to the carbon at the point ofattachment is optionally substituted by R⁹, the other carbon adjacent tothe carbon at the point of attachment is optionally substituted by R¹³,a carbon adjacent to R⁹ and two atoms from the carbon at the point ofattachment is optionally substituted by R¹⁰, a carbon adjacent to R¹³and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹², and any carbon adjacent to both R¹⁰ and R¹² isoptionally substituted by R¹¹;

[0220] K is CHR^(4a) wherein R^(4a) is selected from the groupconsisting of hydrido, hydroxyalkyl, alkyl, alkoxyalkyl, alkylthioalkyl,and haloalkyl;

[0221] E⁰ is selected from the group consisting of a covalent singlebond, C(O)N(H), (H)NC(O), (R⁷)NS(O)₂, and S(O)₂N(R⁷);

[0222] Y⁰ is formula (IV):

[0223]  wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from thegroup consisting of C, N, O, S and a covalent bond with the provisosthat no more than one is a covalent bond, K² is C, no more than one ofD⁵, D⁶, J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S,one of D⁵ D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵,and J⁶ are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ are N,with the provisos that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each independentlyselected to maintain the tetravalent nature of carbon, trivalent natureof nitrogen, the divalent nature of sulfur, and the divalent nature ofoxygen;

[0224] R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio,alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo,haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

[0225] R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no morethan one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b) isQ^(be);

[0226] Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)wherein Q^(be) is hydrido, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴,with the provisos that no more than one of R²⁰ and R²¹ is hydroxy,amino, alkylamino, or dialkylamino at the same time and that no morethan one of R²³ and R²⁴ is hydroxy, amino, alkylamino, or dialkylaminoat the same time;

[0227] R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected fromthe group consisting of hydrido, alkyl, hydroxy, amino, alkylamino anddialkylamino;

[0228] Q^(s) is selected from the group consisting of a single covalentbond, (CR³⁷R³⁸)_(b) wherein b is an integer selected from 1 through 4,and (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d are integersindependently selected from 1 through 3 and W¹ is selected from thegroup consisting of C(O)N(R¹⁴), (R¹⁴)NC(O), S(O), S(O)₂, S(O)₂N(R¹⁴),N(R¹⁴)S(O)₂, and N(R¹⁴), with the provisos that R¹⁴ is selected fromother than halo when directly bonded to N and that (CR³⁷R³⁸)_(b), and(CH(R¹⁴))_(c) are bonded to E⁰;

[0229] R¹⁴ is selected from the group consisting of hydrido, halo,alkyl, and haloalkyl;

[0230] R³⁷ and R³⁸ are independently selected from the group consistingof hydrido, alkyl, and haloalkyl;

[0231] R³⁸ is optionally selected from the group consisting of aroyl andheteroaroyl;

[0232] Y⁰ is optionally Q^(b)—Q^(ss) wherein Q^(ss) is(CH(R¹⁴))_(e)—W²—(CH(R¹⁵))_(h), wherein e and h are integersindependently selected from 1 through 2 and W² is CR^(4a)═CH with theproviso that (CH(R¹⁴))_(e) is bonded to E⁰.

[0233] In an even more preferred embodiment of compounds of Formula I ora pharmaceutically acceptable salt thereof,

[0234] J^(a) and J^(b) are each O;

[0235] B is selected from the group consisting of aryl and heteroarylwherein a carbon adjacent to the carbon at the point of attachment isoptionally substituted by R³², the other carbon adjacent to the carbonat the point of attachment is optionally substituted by R³⁶, a carbonadjacent to R³² and two atoms from the carbon at the point of attachmentis optionally substituted by R³³, a carbon adjacent to R³⁶ and two atomsfrom the carbon at the point of attachment is optionally substituted byR³⁵, and any carbon adjacent to both R³³ and R³⁵ is optionallysubstituted by R³⁴;

[0236] R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from thegroup consisting of hydrido, acetamido, haloacetamido, amidino,guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino,alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,carboalkoxy, carboxy, carboxamido, cyano, and Q^(b);

[0237] A is selected from the group consisting of single covalent bondand (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected from 0through 1, pa is an integer selected from 0 through 3, and W⁷ isselected from the group consisting of (R⁷)NC(O) and N(R⁷);

[0238] R⁷ is selected from the group consisting of hydrido, hydroxy andalkyl

[0239] R¹⁵ is selected from the group consisting of hydrido, halo, alkyland haloalkyl;

[0240] Ψ is NH;

[0241] M is selected from the group consisting of N and R¹—C;

[0242] R¹ is selected from the group consisting of hydrido, hydroxy,hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl,alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy,and halo;

[0243] R² is Z⁰—Q;

[0244] Z⁰ is selected from the group consisting of a covalent singlebond, O, S, NH, and CH₂;

[0245] Q is selected from the group consisting of aryl and heteroarylwherein a carbon adjacent to the carbon at the point of attachment isoptionally substituted by R⁹, the other carbon adjacent to the carbon atthe point of attachment is optionally substituted by R¹³, a carbonadjacent to R⁹ and two atoms from the carbon at the point of attachmentis optionally substituted by R¹⁰, a carbon adjacent to R¹³ and two atomsfrom the carbon at the point of attachment is optionally substituted byR¹², and any carbon adjacent to both R¹⁰ and R¹² is optionallysubstituted by R¹¹;

[0246] R⁹, R¹¹, and R¹³ are independently selected from the groupconsisting of hydrido, hydroxy, amino, amidino, guanidino, loweralkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl,amidosulfonyl, monoalkyl amidosulfonyl, alkyl, alkoxy, halo, haloalkyl,haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;

[0247] R¹⁰ and R¹² are independently selected from the group consistingof hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy,hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido,amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl,hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl,aminocarbonyl, halo, haloalkyl, and cyano;

[0248] K is CH₂;

[0249] E⁰ is C(O)N(H);

[0250] Y⁰ is formula (IV):

[0251]  wherein D⁵, D⁶, J⁵ and J⁶ are independently selected from thegroup consisting of C, N, O, S and a covalent bond with the provisosthat no more than one is a covalent bond, K² is C, no more than one ofD⁵, D⁶, J⁵, and J⁶ is optionally O, no more than one of D⁵, D⁶, J⁵,andJ⁶ is optionally S, one of D⁵, D⁶, J⁵, and J⁶ must be a covalent bondwhen two of D⁵, D⁶, J⁵, and J⁶ are O and S, and no more than four of D⁵,D⁶, J⁵, and J⁶ are N;

[0252] R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl,alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

[0253] R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no morethan one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b) isQ^(be);

[0254] Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)wherein Q^(be) is hydrido, and C(NR²⁵)NR²³R²⁴, with the provisos that nomore than one of R²⁰ and R²¹ is hydroxy at the same time and that nomore than one of R²³ and R²⁴ is hydroxy at the same time;

[0255] R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from thegroup consisting of hydrido, alkyl, and hydroxy;

[0256] Q^(s) is selected from the group consisting of a single covalentbond, CH₂, and CH₂CH₂.

[0257] In another even more preferred embodiment of compounds of FormulaI or a pharmaceutically acceptable salt thereof,

[0258] J^(a) and J^(b) are each O;

[0259] B is optionally selected from the group consisting of hydrido,C2-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, whereineach member of group B is optionally substituted at any carbon up to andincluding 6 atoms from the point of attachment of B to A with one ormore of the group consisting of R³², R³³, R³⁴, R³⁵, and R³⁶;

[0260] R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from thegroup consisting of hydrido, acetamido, haloacetamido, amidino,guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino,alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,carboalkoxy, carboxy, carboxamido, cyano, and Q^(b);

[0261] A is selected from the group consisting of single covalent bondand (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected from 0through 1, pa is an integer selected from 0 through 3, and W⁷ isselected from the group consisting of (R⁷)NC(O) and N(R⁷);

[0262] R⁷ is selected from the group consisting of hydrido, hydroxy andalkyl;

[0263] R¹⁵ is selected from the group consisting of hydrido, halo, alkyland haloalkyl;

[0264] Ψ is NH;

[0265] M is selected from the group consisting of N and R¹—C;

[0266] R¹ is selected from the group consisting of hydrido, hydroxy,hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl,alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy,and halo;

[0267] R² is Z⁰—Q;

[0268] Z⁰ is selected from the group consisting of a covalent singlebond, O, S, NH, and CH₂;

[0269] Q is selected from the group consisting of aryl and heteroarylwherein a carbon adjacent to the carbon at the point of attachment isoptionally substituted by R⁹, the other carbon adjacent to the carbon atthe point of attachment is optionally substituted by R¹³, a carbonadjacent to R⁹ and two atoms from the carbon at the point of attachmentis optionally substituted by R¹⁰, a carbon adjacent to R¹³ and two atomsfrom the carbon at the point of attachment is optionally substituted byR¹², and any carbon adjacent to both R¹⁰ and R¹² is optionallysubstituted by R¹¹;

[0270] R⁹, R¹¹, and R¹³ are independently selected from the groupconsisting of hydrido, hydroxy, amino, amidino, guanidino, loweralkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl,amidosulfonyl, monoalkyl amidosulfonyl, alkyl, alkoxy, halo, haloalkyl,haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;

[0271] R¹⁰ and R¹² are independently selected from the group consistingof hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy,hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido,amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl,hydroxyalkyl, alkylenylamino, carboalkoxy, carboxy, carboxyalkyl,aminocarbonyl, halo haloalkyl, and cyano;

[0272] K is CH₂;

[0273] E⁰ is C(O)N(H);

[0274] Y⁰ is formula (IV);

[0275]  wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from thegroup consisting of C, N, O, S and a covalent bond with the provisosthat no more than one is a covalent bond, K² is C, no more than one ofD⁵, D⁶, J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S,one of D⁵, D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶,J⁵, and J⁶ are O and S, and no more than four of D⁵, D⁶, J⁵ and J⁶ areN, with the provisos that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each independentlyselected to maintain the tetravalent nature of carbon, trivalent natureof nitrogen, the divalent nature of sulfur, and the divalent nature ofoxygen;

[0276] R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl,alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, alkylenylamino, and cyano;

[0277] R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no morethan one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b) isQ^(be);

[0278] Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)wherein Q^(be) is hydrido, C(NR²⁵)NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),with the provisos that no more than one of R²⁰ and R²¹ is hydroxy at thesame time and that no more than one of R²³ and R²⁴ is hydroxy at thesame time;

[0279] R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected fromthe group consisting of hydrido, alkyl, and hydroxy;

[0280] Q^(s) is selected from the group consisting of a single covalentbond, CH₂, and CH₂CH₂.

[0281] In still another even more preferred embodiment of compounds ofFormula I or a pharmaceutically acceptable salt thereof,

[0282] J^(a) and J^(b) are each O;

[0283] B is optionally selected from the group consisting of C3-C7cycloalkyl and C4-C6 saturated heterocyclyl, wherein each ring carbon isoptionally substituted with R³³, a ring carbon other than the ringcarbon at the point of attachment of B to A is optionally substitutedwith oxo provided that no more than one ring carbon is substituted byoxo at the same time, ring carbons and a nitrogen adjacent to the carbonatom at the point of attachment are optionally substituted with R⁹ orR¹³, a ring carbon or nitrogen adjacent to the R⁹ position and two atomsfrom the point of attachment is optionally substituted with R¹⁰, a ringcarbon or nitrogen adjacent to the R¹³ position and two atoms from thepoint of attachment is optionally substituted with R¹², a ring carbon ornitrogen three atoms from the point of attachment and adjacent to theR¹⁰ position is optionally substituted with R¹¹, a ring carbon ornitrogen three atoms from the point of attachment and adjacent to theR¹² position is optionally substituted with R³³, and a ring carbon ornitrogen four atoms from the point of attachment and adjacent to the R¹¹and R³³ positions is optionally substituted with R³⁴;

[0284] R⁹, R¹¹, and R¹³ are independently selected from the groupconsisting of hydrido, hydroxy, amino, amidino, guanidino, loweralkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl,amidosulfonyl, monoalkyl amidosulfonyl, alkyl, alkoxy, halo, haloalkyl,haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;

[0285] R¹⁰ and R¹² are independently selected from the group consistingof hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy,hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido,amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl,hydroxyalkyl, alkylenylamino, carboalkoxy, carboxy, carboxyalkyl,aminocarbonyl, halo, haloalkyl, and cyano;

[0286] R³³ and R³⁴ are independently selected from the group consistingof hydrido, acetamido, haloacetamido, amidino, guanidino, alkoxy,hydroxy, amino, alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl,monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, andQ^(b);

[0287] A is selected from the group consisting of single covalent bondand (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected from 0through 1, pa is an integer selected from 0 through 3, and W⁷ isselected from the group consisting of(R⁷)NC(O) and N(R⁷);

[0288] R⁷ is selected from the group consisting of hydrido, hydroxy andalkyl;

[0289] R¹⁵ is selected from the group consisting of hydrido, halo,alkyl, and haloalkyl;

[0290] Ψ is NH;

[0291] M is selected from the group consisting of N and R¹—C;

[0292] R¹ is selected from the group consisting of hydrido, hydroxy,hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl,alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy,and halo;

[0293] R² is Z⁰—Q;

[0294] Z⁰ is selected from the group consisting of a covalent singlebond, O, S, NH, and CH₂;

[0295] Q is selected from the group consisting of aryl and heteroarylwherein a carbon adjacent to the carbon at the point of attachment isoptionally substituted by R⁹, the other carbon adjacent to the carbon atthe point of attachment is optionally substituted by R¹³, a carbonadjacent to R⁹ and two atoms from the carbon at the point of attachmentis optionally substituted by R¹⁰, a carbon adjacent to R¹³ and two atomsfrom the carbon at the point of attachment is optionally substituted byR¹², and any carbon adjacent to both R¹⁰ and R¹² is optionallysubstituted by R¹¹;

[0296] K is CH₂;

[0297] E⁰ is C(O)N(H);

[0298] Y⁰ is formula (IV):

[0299]  wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from thegroup consisting of C, N, O, S and a covalent bond with the provisosthat no more than one is a covalent bond, K² is C, no more than one ofD⁵, D⁶, J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S,one of D⁵, D⁶, J⁵ and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵,and J⁶ are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ are N,with the provisos that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each independentlyselected to maintain the tetravalent nature of carbon, trivalent natureof nitrogen, the divalent nature of sulfur, and the divalent nature ofoxygen;

[0300] R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl,alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, alkylenylamino, and cyano;

[0301] R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no morethan one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b) isQ^(be);

[0302] Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)wherein Q^(be) is hydrido, and C(NR²⁵)NR²³R²⁴, with the provisos that nomore than one of R²⁰ and R²¹ is hydroxy at the same time and that nomore than one of R²³ and R²⁴ is hydroxy at the same time;

[0303] R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from thegroup consisting of hydrido, alkyl, and hydroxy;

[0304] Q^(s) is selected from the group consisting of a single covalentbond, CH₂, and CH₂CH₂.

[0305] In a most preferred embodiment of compounds of Formula I or apharmaceutically acceptable salt thereof,

[0306] J^(a) and J^(b) are each O;

[0307] B is selected from the group consisting of aryl and heteroarylwherein a carbon adjacent to the carbon at the point of attachment isoptionally substituted by R³², the other carbon adjacent to the carbonat the point of attachment is optionally substituted by R³⁶, a carbonadjacent to R³² and two atoms from the carbon at the point of attachmentis optionally substituted by R³³, a carbon adjacent to R³⁶ and two atomsfrom the carbon at the point of attachment is optionally substituted byR³⁵, and any carbon adjacent to both R³³ and R³⁵ is optionallysubstituted by R³⁴;

[0308] R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from thegroup consisting of hydrido, acetamido, haloacetamido, amidino,guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino,alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,carboalkoxy, carboxy, carboxamido, cyano, and Q^(b);

[0309] A is selected from the group consisting of single covalent bondand (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected from 0through 1, pa is an integer selected from 0 through 3, and W⁷ is N(R⁷);

[0310] R⁷ is selected from the group consisting of hydrido and alkyl;

[0311] R¹⁵ is selected from the group consisting of hydrido, halo,alkyl, and haloalkyl;

[0312] Ψ is NH;

[0313] M is selected from the group consisting of N and R¹—C;

[0314] R¹ is selected from the group consisting of hydrido, hydroxy,hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl,alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy,and halo;

[0315] R² is Z⁰—Q;

[0316] Z⁰ is a covalent single bond;

[0317] Q is selected from the group consisting of aryl and heteroarylwherein a carbon adjacent to the carbon at the point of attachment isoptionally substituted by R⁹, the other carbon adjacent to the carbon atthe point of attachment is optionally substituted by R¹³, a carbonadjacent to R⁹ and two atoms from the carbon at the point of attachmentis optionally substituted by R¹⁰, a carbon adjacent to R¹³ and two atomsfrom the carbon at the point of attachment is optionally substituted byR¹², and any carbon adjacent to both R¹⁰ and R¹² is optionallysubstituted by R¹¹;

[0318] R⁹, R¹¹, and R¹³ are independently selected from the groupconsisting of hydrido, hydroxy, amino, amidino, guanidino, loweralkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl,amidosulfonyl, monoalkyl amidosulfonyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;

[0319] R¹⁰ and R¹² are independently selected from the group consistingof hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy,alkoxyamino, aminoalkyl, hydroxy, amino, lower alkylamino,alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy,carboxy, carboxyalkyl, carboxyamido, and cyano;

[0320] K is CH₂;

[0321] E⁰ is C(O)N(H);

[0322] Y⁰ is formula (IV):

[0323]  wherein D⁵, D⁶, J⁵ and J⁶ are independently selected from thegroup consisting of C, N, O, S and a covalent bond with the provisosthat no more than one is a covalent bond, K² is C, no more than one ofD⁵, D⁶, J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S,one of D⁵, D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶,J⁵, and J⁶ are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ areN;

[0324] R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl,alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

[0325] R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no morethan one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b) isQ^(be);

[0326] Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)wherein Q^(be) is hydrido, and C(NR²⁵)NR²³R²⁴;

[0327] R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from thegroup consisting of hydrido and alkyl;

[0328] Q^(s) is CH₂.

[0329] In another most preferred embodiment of compounds of Formula I ora pharmaceutically acceptable salt thereof,

[0330] J^(a) and J^(b) are each O;

[0331] B is optionally selected from the group consisting of hydrido,C2-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8 haloalkyl, whereineach member of group B is optionally substituted at any carbon up to andincluding 6 atoms from the point of attachment of B to A with one ormore of the group consisting of R³², R³³, R³⁴, R³⁵, and R³⁶;

[0332] R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from thegroup consisting of hydrido, acetamido, haloacetamido, amidino,guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino,alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,carboalkoxy, carboxy, carboxamido, cyano,and Q^(b);

[0333] A is selected from the group consisting of single covalent bondand (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected from 0through 1, pa is an integer selected from 0 through 3, and W⁷ is N(R⁷);

[0334] R⁷ is selected from the group consisting of hydrido and alkyl;

[0335] R¹⁵ is selected from the group consisting of hydrido, halo,alkyl, and haloalkyl;

[0336] Ψ is NH;

[0337] M is selected from the group consisting of N and R¹—C;

[0338] R¹ is selected from the group consisting of hydrido, hydroxy,hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl,alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy,and halo;

[0339] R² is Z⁰—Q;

[0340] Z⁰ is a covalent single bond;

[0341] Q is selected from the group consisting of aryl and heteroarylwherein a carbon adjacent to the carbon at the point of attachment isoptionally substituted by R⁹, the other carbon adjacent to the carbon atthe point of attachment is optionally substituted by R¹³, a carbonadjacent to R⁹ and two atoms from the carbon at the point of attachmentis optionally substituted by R¹⁰, a carbon adjacent to R¹³ and two atomsfrom the carbon at the point of attachment is optionally substituted byR¹², and any carbon adjacent to both R¹⁰ and R¹² is optionallysubstituted by R¹¹;

[0342] R⁹, R¹¹, and R¹³ are independently selected from the groupconsisting of hydrido, hydroxy, amino, amidino, guanidino, loweralkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl,amidosulfonyl, monoalkyl amidosulfonyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;

[0343] R¹⁰ and R¹² are independently selected from the group consistingof hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy,alkoxyamino, aminoalkyl, hydroxy, amino, lower alkylamino,alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy,carboxy, carboxyalkyl, carboxyamido, and cyano;

[0344] K is CH₂;

[0345] E⁰ is C(O)N(H);

[0346] Y⁰ is formula (IV):

[0347]  wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from thegroup consisting of C, N, O, S and a covalent bond with the provisosthat no more than one is a covalent bond, K² is C, no more than one ofD⁵, D⁶, J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S,one of D⁵, D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶,J⁵, and J⁶ are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ areN, with the provisos that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each independentlyselected to maintain the tetravalent nature of carbon, trivalent natureof nitrogen, the divalent nature of sulfur, and the divalent nature ofoxygen;

[0348] R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl,alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano;

[0349] R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no morethan one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b) isQ^(be);

[0350] Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)wherein Q^(be) is hydrido, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴;

[0351] R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected fromthe group consisting of hydrido and alkyl;

[0352] Q^(s) is CH₂.

[0353] In still another most preferred embodiment of compounds ofFormula I or a pharmaceutically acceptable salt thereof,

[0354] J^(a) and J^(b) are each O;

[0355] B is optionally selected from the group consisting of C3-C7cycloalkyl and C4-C6 saturated heterocyclyl, wherein each ring carbon isoptionally substituted with R³³, a ring carbon other than the ringcarbon at the point of attachment of B to A is optionally substitutedwith oxo provided that no more than one ring carbon is substituted byoxo at the same time, ring carbons and a nitrogen adjacent to the carbonatom at the point of attachment are optionally substituted with R⁹ orR¹³, a ring carbon or nitrogen adjacent to the R⁹ position and two atomsfrom the point of attachment is optionally substituted with R¹⁰, a ringcarbon or nitrogen adjacent to the R¹³ position and two atoms from thepoint of attachment is optionally substituted with R¹², a ring carbon ornitrogen three atoms from the point of attachment and adjacent to theR¹⁰ position is optionally substituted with R¹¹, a ring carbon ornitrogen three atoms from the point of attachment and adjacent to theR¹² position is optionally substituted with R³³, and a ring carbon ornitrogen four atoms from the point of attachment and adjacent to the R¹¹and R³³ positions is optionally substituted with R³⁴;

[0356] R⁹, R¹¹, and R¹³ are independently selected from the groupconsisting of hydrido, hydroxy, amino, amidino, guanidino, loweralkylamino, alkylthio, alkoxy, alkylsulfinyl, alkylsulfonyl,amidosulfonyl, monoalkyl amidosulfonyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano;

[0357] R¹⁰ and R¹² are independently selected from the group consistingof hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy,alkoxyamino, aminoalkyl, hydroxy, amino, lower alkylamino,alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl, carboalkoxy,carboxy, carboxyalkyl, carboxyamido, and cyano;

[0358] R³³ and R³⁴ are independently selected from the group consistingof hydrido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino,lower alkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl,dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,carboalkoxy, carboxy, carboxamido, and cyano;

[0359] R³³ is optionally Q^(b);

[0360] A is selected from the group consisting of single covalent bondand (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected from 0through 1, pa is an integer selected from 0 through 3, and W⁷ is N(R⁷);

[0361] R⁷ is seleted from the group consisting of hydrido, hydroxy andalkyl;

[0362] R¹⁵ is selected from the group consisting of hydrido, halo,alkyl, and haloalkyl;

[0363] Ψ is NH;

[0364] M is selected from the group consisting of N and R¹—C;

[0365] R¹ is selected from the group consisting of hydrido, hydroxy,hydroxyamino, amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl,alkylamino, aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy,and halo;

[0366] R² is Z⁰—Q;

[0367] Z⁰ is a covalent single bond;

[0368] Q is selected from the group consisting of aryl and heteroarylwherein a carbon adjacent to the carbon at the point of attachment isoptionally substituted by R⁹, the other carbon adjacent to the carbon atthe point of attachment is optionally substituted by R¹³, a carbonadjacent to R⁹ and two atoms from the carbon at the point of attachmentis optionally substituted by R¹⁰, a carbon adjacent to R¹³ and two atomsfrom the carbon at the point of attachment is optionally substituted byR¹², and any carbon adjacent to both R¹⁰ and R¹² is optionallysubstituted by R¹¹;

[0369] K is CH₂;

[0370] E⁰ is C(O)N(H);

[0371] Y⁰ is formula (IV):

[0372]  wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from thegroup consisting of C, N, O, S and a covalent bond with the provisosthat no more than one is a covalent bond, K² is C, no more than one ofD⁵, D⁶, J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S,one of D⁵, D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶,J⁵, and J⁶ are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ areN, with the provisos that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are each independentlyselected to maintain the tetravalent nature of carbon, trivalent natureof nitrogen, the divalent nature of sulfur, and the divalent nature ofoxygen;

[0373] R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, haloalkylthio,alkoxy, hydroxy, amino, lower alkylamino, alkylthio, alkylsulfinyl,alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, alkylenylamino, and cyano;

[0374] R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no morethan one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b) isQ^(be);

[0375] Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)wherein Q^(be) is hydrido, and C(NR²⁵)NR²³R²⁴;

[0376] R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from thegroup consisting of hydrido and alkyl;

[0377] Q^(s) is CH₂.

[0378] In a preferred specific embodiment of Formula I, compounds havethe Formula I-S:

[0379] or a pharmaceutically acceptable salt thereof, wherein;

[0380] B is selected from the group consisting of phenyl, 2-thienyl,3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 1,2,4-triazol-3-yl,1,2,4-triazol-5-yl, 1,2,4oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl,1,3,4-oxadiazol-3-yl, 1,3,4-oxadiazol-5-yl, 3-isothiazolyl,5-isothiazolyl, 2-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl,2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl,4pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl,1,3,5-triazin-2-yl, 1,2,4triazin-3-yl, 1,2,4-triazin-5-yl,1,2,4-triazin-6-yl, 1,2,3-triazin-4-yl, and 1,2,3-triazin-5-yl, whereina carbon adjacent to the carbon at the point of attachment is optionallysubstituted by R³², the other carbon adjacent to the carbon at the pointof attachment is optionally substituted by R³⁶, a carbon adjacent to R³²and two atoms from the carbon at the point of attachment is optionallysubstituted by R³³, a carbon adjacent to R³⁶ and two atoms from thecarbon at the point of attachment is optionally substituted by R³⁵, andany carbon adjacent to both R³³ and R³⁵ is optionally substituted byR³⁴;

[0381] R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from thegroup consisting of hydrido, amidino, guanidino, carboxy, methyl, ethyl,isopropyl, propyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, nitro,aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino,N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl, propanoyl,trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl, 1-hydroxyethyl,2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, carboxymethyl,methoxycarbonyl, ethoxycarbonyl, aminocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, cyano, and Q^(b);

[0382] B is selected from the group consisting of hydrido,trimethylsilyl, ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl,2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl,2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 4-pentenyl,2-pentynyl, 3-pentynyl, 2-pentyl, 1-methyl-2-butenyl,1-methyl-3-butenyl, 1-methyl-2-butynyl, 3-pentyl, 1-ethyl-2-propenyl,2-methylbutyl, 2-methyl-2-butenyl, 2-methyl-3-butenyl,2-methyl-3-butynyl, 3-methylbutyl, 3-methyl-2-butenyl,3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl,2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, 1-methyl-2-pentenyl,1-methyl-3-pentenyl, 1-methyl-4-pentenyl, 1-methyl-2-pentynyl,1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl,1-propyl-2-propenyl, 1-ethyl-2-butynyl, 1-heptyl, 2-heptenyl,3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptynyl, 3-heptynyl,4-heptynyl, 5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl,1-methyl-3-hexenyl, 1-methyl-4-hexenyl, 1-methyl-5-hexenyl,1-methyl-2-hexynyl, 1-methyl-3-hexynyl, 1-methyl-4-hexynyl, 3-heptyl,1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl,1-butyl-2-propenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 1-octyl,2-octenyl, 3-octenyl, 4octenyl, 5-octenyl, 6-octenyl, 7-octenyl,2-octynyl, 3-octynyl, 4-octynyl, 5-octynyl, 6-octynyl, 2-octyl,1-methyl-2-heptenyl, 1-methyl-3-heptenyl, 1-methyl-4-heptenyl,1-methyl-5-heptenyl, 1-methyl-6-heptenyl, 1-methyl-2-heptynyl,1-methyl-3-heptynyl, 1-methyl-4-heptenyl, 1-methyl-5-heptenyl,1-methyl-6-heptenyl, 1-methyl-2-heptenyl, 1-methyl-3-heptynyl,1-methyl-4heptynyl, 1-methyl-5-heptynyl, 3-octyl, 1-ethyl-2-hexenyl,1-ethyl-3-hexenyl, 1-ethylthexenyl, 1-ethyl-2-hexynyl,1-ethyl-3-hexynyl, 1-ethyl-4-hexynyl, 1-ethyl-5-hexenyl,1-pentyl-2-propenyl, 4-octyl, 1-propyl-2-pentenyl, 1-propyl-3-pentenyl,1-propyl-4-pentenyl, 1-butyl-2-butenyl, 1-propyl-2-pentynyl,1-propyl-3-pentynyl, 1-butyl-2-butynyl, 1-butyl-3-butenyl,2,2,2-trifluoroethyl, 2,2-difluoropropyl,4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl,5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein eachmember of group B is optionally substituted at any carbon up to andincluding 5 atoms from the point of attachment of B to A with one ormore of the group consisting of R³², R³³, R³⁴, R³⁵, and R³⁶;

[0383] B is optionally selected from the group consisting ofcyclopropyl, cyclobutyl, oxetan-2-yl, oxetan-3-yl, azetidin-1-yl,azetidin-2-yl, azetidin-3-yl, thiaetan-2-yl, thiaetan-3-yl, cyclopentyl,cyclohexyl, adamantyl, norbornyl, 3-trifluoromethylnorbornyl,7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl, cycloheptyl,cyclooctyl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 1-piperazinyl,2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl,4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl,2-dioxanyl, 4H-2-pyranyl, 4H-3-pyranyl, 4H-4-pyranyl,4H-pyran-4-one-2-yl, 4H-pyran-4-one-3-yl, 2-tetrahydrofuranyl,3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl,4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl,wherein each ring carbon is optionally substituted with R³³, ringcarbons and a nitrogen adjacent to the carbon atom at the point ofattachment is optionally substituted with R⁹ or R¹³, a ring carbon ornitrogen adjacent to the R⁹ position and two atoms from the point ofattachment is optionally substituted with R¹⁰, and a ring carbon ornitrogen adjacent to the R¹³ position and two atoms from the point ofattachment is optionally substituted with R¹²;

[0384] R⁹, R¹⁰, R¹¹, R¹², and R¹³ are independently selected from thegroup consisting of hydrido, amidino, guanidino, carboxy, carboxymethyl,methyl, ethyl, isopropyl, propyl, methoxy, ethoxy, isopropoxy, propoxy,hydroxy, amino, methoxyamino, ethoxyamino, acetamido,trifluoroacetamido, nitro, aminomethyl, 1-aminoethyl, 2-aminoethyl,N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio,isopropylthio, trifluoromethylthio, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl,propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,2,2,2-trifluoro-1-trifluoromethyl-1-hydroxyethyl, carboxymethyl,methoxycarbonyl, ethoxycarbonyl, aminocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, and cyano;

[0385] A is selected from the group consisting of single covalent bond,O, S, NH, N(CH₃), N(OH), C(O), CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O),C(O)NH, C(O)N(CH₃), CF₃CC(O), C(O)CCH₃, C(O)CCF₃, CH₂C(O), (O)CCH₂,CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, CF₃CHCH₂, CH₃CC(O)CH₂, CF₃CC(O)CH₂,CH₂C(O)CCH₃, CH₂C(O)CCF₃, CH₂CH₂C(O), and CH₂(O) CCH₂;

[0386] A is optionally selected from the group consisting of CH₂N(CH₃),CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), and CH₂CH₂N(CH₂CH₃) with the proviso that Bis hydrido;

[0387] M is selected from the group consisting of N and R¹—C;

[0388] R¹ is selected from the group consisting of hydrido, hydroxy,amino, thiol, amidino, hydroxyamino, aminomethyl, 1-aminoethyl,2-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl,isopropyl, propyl, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, methoxy, ethoxy,propoxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino,ethoxyamino, methylthio, ethylthio, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo;

[0389] R² is Z⁰—Q;

[0390] Z⁰ is selected from the group consisting of covalent single bond,O, S, NH, CH₂, CH₂CH₂, CH(OH), CH(NH₂), CH₂CH(OH), CH₂CHNH₂, CH(OH)CH₂,and CH(NH₂)CH₂;

[0391] Q is selected from the group consisting of phenyl, 2-thienyl,3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 1,2,4-triazol-3-yl,1,2,4-triazol-5-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl,1,3,4oxadiazol-3-yl, 1,3,4-oxadiazol-5-yl, 3-isothiazolyl,5-isothiazolyl, 2-oxazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl,2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl,4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl,1,3,5-triazin-2-yl, 1,2,4-triazin-3-yl, 1,2,4-triazin-5-yl,1,2,4-triazin-6-yl, 1,2,3-triazin-4yl, and 1,2,3-triazin-5-yl, wherein acarbon adjacent to the carbon at the point of attachment is optionallysubstituted by R⁹, the other carbon adjacent to the carbon at the pointof attachment is optionally substituted by R¹³, a carbon adjacent to R⁹and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹⁰, a carbon adjacent to R¹³ and two atoms from thecarbon at the point of attachment is optionally substituted by R¹², andany carbon adjacent to both R¹⁰ and R¹² is optionally substituted byR¹¹;

[0392] K is CHR^(4a) wherein R^(4a) is selected from the groupconsisting of methyl, ethyl, propyl, isopropyl, hydroxymethyl,1-hydroxyehtyl, methoxymethyl, triflouromethyl, pentafluoroethyl,2,2,2-triflouromethyl, methylthiomethyl, and hydrido;

[0393] E⁰ is a covalent single bond, C(O)N(H), (H)NC(O), and S(O)₂N(H);

[0394] Y⁰ is selected from the group of formulas consisting of:

[0395]  R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, methyl, ethyl, isopropyl, propyl, amidino,guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy,amino, methoxyamino, ethoxyamino, aminomethyl, 1-aminoethyl,2-aminoethyl, N-N-methylamino, dimethylamino, N-ethylamino, methylthio,ethylthio, isopropylthio, trifluoromethylthio, methylsulfinyl,ethylsulfinyl, methylsulfonyl, ethylsulfonyl, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, acetyl,propanoyl, trifluoroacetyl, pentafluoropropanoyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, andcyano;

[0396] R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no morethan one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b) isQ^(be);

[0397] Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)wherein Q^(be) is hydrido, C(NR²⁵)NR²³R²⁴ and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),with the proviso that no more than one of R²⁰ and R²¹ is hydroxy,N-methylamino, and N,N-dimethylamino at the same time and that no morethan one of R²³ and R²⁴ is hydroxy, N-methylamino, and N,N-dimethylaminoat the same time;

[0398] R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected fromthe group consisting of hydrido, methyl, ethyl, propyl, butyl,isopropyl, hydroxy, 2-aminoethyl, 2-(N-methylamino)ethyl, and2-(N,N-dimethylamino)ethyl;

[0399] Q^(s) is selected from the group consisting of a single covalentbond, CH₂, CH₂CH₂, CH₃CH, CF₃CH, CH₃CHCH₂, CF₃CHCH₂, CH₂(CH₃)CH, CH═CH,CF═CH, C(CH₃)═CH, CH═CHCH₂, CF═CHCH₂, C(CH₃)═CHCH₂, CH₂CH═CH, CH₂CF═CH,CH₂C(CH₃)═CH, CH₂CH═CHCH₂, CH₂CF═CHCH₂, CH₂C(CH₃)═CHCH₂, CH₂CH═CHCH₂CH₂,CH₂CF═CHCH₂CH₂, and CH₂C(CH₃)═CHCH₂CH₂.

[0400] In a more preferred specific embodiment of Formula I, compoundshave the Formula I-MPS wherein B is an aromatic:

[0401] (I-MPS wherein B is aromatic)

[0402] or a pharmaceutically acceptable salt thereof, wherein;

[0403] B is selected from the group consisting of phenyl, 2-thienyl,3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl,5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl,2-pyrimidinyl, 4pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4pyridazinyl,and 1,3,5-triazin-2-yl, wherein a carbon adjacent to the carbon at thepoint of attachment is optionally substituted by R³², the other carbonadjacent to the carbon at the point of attachment is optionallysubstituted by R³⁶, a carbon adjacent to R³² and two atoms from thecarbon at the point of attachment is optionally substituted by R³³, acarbon adjacent to R³⁶ and two atoms from the carbon at the point ofattachment is optionally substituted by R³⁵, and any carbon adjacent toboth R³³ and R³⁵ is optionally substituted by R³⁴;

[0404] R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from thegroup consisting of hydrido, amidino, guanidino, carboxy, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,acetamido, trifluoroacetamido, N-methylamino, dimethylamino,N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano,and Q^(b);

[0405] A is selected from the group consisting of single covalent bond,NH, N(CH₃), N(OH), CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH,C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂;

[0406] Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)wherein Q^(be) is hydrido, and C(NR²⁵)NR²³R²⁴, with the provisos that nomore than one of R²⁰ and R²¹ is hydroxy at the same time and that nomore than one of R²³ and R²⁴ is hydroxy at the same time;

[0407] R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from thegroup consisting of hydrido, methyl, ethyl, propyl, butyl, isopropyl,and hydroxy;

[0408] Q^(s) is selected from the group consisting of a single covalentbond, CH₂, and CH₂CH₂.

[0409] In another more preferred specific embodiment of Formula I,compounds have the Formula I-MPS wherein B is a non-cyclic substituent:

[0410] wherein B is a non-cyclic substituent)

[0411] or a pharmaceutically acceptable salt thereof, wherein;

[0412] B is selected from the group consisting of hydrido, ethyl,2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butenyl, 3-butenyl,2-butynyl, sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl, 1-pentyl,2-pentenyl, 3-pentenyl, 4-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl,1-methyl-2-butenyl, 1-methyl -3-butenyl, 1-methyl-2-butynyl, 3-pentyl,1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl,2-methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl,3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl,4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-4-pentenyl,1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl,1-ethyl-3-butenyl, 1-propyl -2-propenyl, 1-ethyl-2-butynyl, 1-heptyl,2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptynyl,3-heptynyl, 4heptynyl, 5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl,1-methyl-3-hexenyl, 1-methyl-4-hexenyl, 1-methyl-5hexenyl,1-methyl-2-hexynyl, 1-methyl-3-hexynyl, 1-methyl -4-hexynyl, 3-heptyl,1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl,1-butyl-2-propenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl,2,2,2-trifluoroethyl, 2,2-difluoropropyl,4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl,5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein eachmember of group B is optionally substituted at any carbon up to andincluding 5 atoms from the point of attachment of B to A with one ormore of the group consisting of R³², R³³, R³⁴, R³⁵, and R³⁶;

[0413] R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from thegroup consisting of hydrido, amidino, guanidino, carboxy, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,acetamido, trifluoroacetamido, N-methylamino, dimethylamino,N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl,trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, cyano,and Q^(b);

[0414] A is selected from the group consisting of single covalent bond,NH, N(CH₃), N(OH), CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH,C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂;

[0415] A is optionally selected from the group consisting of CH₂N(CH₃),CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), and CH₂CH₂N(CH₂CH₃) with the proviso that Bis hydrido;

[0416] Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be),wherein Q^(be) is hydrido, C(NR²⁵)NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),with the provisos that no more than one of R²⁰ and R²¹ is hydroxy at thesame time and that no more than one of R²³ and R²⁴ is hydroxy at thesame time;

[0417] R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected fromthe group consisting of hydrido, methyl, ethyl, propyl, butyl,isopropyl, and hydroxy;

[0418] Q^(s) is selected from the group consisting of a single covalentbond, CH₂, and CH₂CH₂.

[0419] In still another more preferred specific embodiment of Formula I,compounds have the Formula I-MPS wherein B is a non-aromatic cyclicsubstituent:

[0420] wherein B is a non-aromatic cyclic substituent)

[0421] or a pharmaceutically acceptable salt thereof, wherein;

[0422] B is optionally selected from the group consisting ofcyclopropyl, cyclobutyl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl,azetidin-3-yl, thiaetan-3-yl, cyclopentyl, cyclohexyl, norbornyl,7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl, cycloheptyl,2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 1-piperazinyl,2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl,4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl,2-dioxanyl, 4H-2-pyranyl, 4H-3-pyranyl, 4H-4pyranyl,4H-pyran-4-one-2-yl, 4H-pyran-4-one-3-yl, 2-tetrahydrofuranyl,3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl,4-tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl,wherein each ring carbon is optionally substituted with R³³, a ringcarbon and a nitrogen adjacent to the carbon atom at the point ofattachment are optionally substituted with R⁹ or R¹³, a ring carbon ornitrogen adjacent to the R⁹ position and two atoms from the point ofattachment is optionally substituted with R¹⁰, and a ring carbon ornitrogen adjacent to the R¹³ position and two atoms from the point ofattachment is optionally substituted with R¹²;

[0423] A is selected from the group consisting of single covalent bond,NH, N(CH₃), N(OH), CH₂, CH₃CH, CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH,C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂, CH₃CHCH₂, and CF₃CHCH₂;

[0424] R³³ is selected from the group consisting of hydrido, amidino,guanidino, carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy,amino, methoxyamino, ethoxyamino, acetamido, trifluoroacetamido,N-methylamino, dimethylamino, N-ethylamino, methylthio, ethylthio,isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, cyano, and Q^(b);

[0425] Q^(b) is selected from the group consisting of NR²⁰ R²¹, Q^(be)wherein Q^(be) is hydrido, and C(NR²⁵)NR²³R²⁴, with the provisos that nomore than one of R²⁰ and R²¹ is hydroxy at the same time and that nomore than one of R²³ and R²⁴ is hydroxy at the same time;

[0426] R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from thegroup consisting of hydrido, methyl, ethyl, propyl, butyl, isopropyl,and hydroxy;

[0427] Q^(s) is selected from the group consisting of a single covalentbond, CH₂, and CH₂CH₂.

[0428] The more preferred specific embodiment (I-MPS) compounds of thepresent invention having the Formula:

[0429] or a pharmaceutically acceptable salt thereof, have commonstructural units, wherein;

[0430] M is selected from the group consisting of N and R¹—C;

[0431] R¹ is selected from the group consisting of hydrido, hydroxy,amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino,dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl,2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo;

[0432] R² is Z⁰—Q;

[0433] Z⁰ is selected from the group consisting of a covalent singlebond, O, S, NH, and CH₂;

[0434] Q is selected from the group consisting of phenyl, 2-thienyl,3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl,5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl,2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl,4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a carbon or nitrogenadjacent to the carbon at the point of attachment is optionallysubstituted by R⁹, the other carbon or nitrogen adjacent to the carbonat the point of attachment is optionally substituted by R¹³, a carbon ornitrogen adjacent to R⁹ and two atoms from the carbon at the point ofattachment is optionally substituted by R¹⁰, a carbon adjacent to R¹³and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹², and any carbon adjacent to both R¹⁰ and R¹² isoptionally substituted by R¹¹;

[0435] R⁹, R¹¹, and R¹³ are independently selected from the groupconsisting of hydrido, amidino, guanidino, carboxy, methyl, ethyl,propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,N-methylamino, N,N-dimethylamino, N-ethylamino, methylthio, ethylthio,isopropylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, and cyano;

[0436] R¹⁰ and R¹² are independently selected from the group consistingof hydrido, amidino, guanidino, carboxy, carboxymethyl, methyl, ethyl,propyl, isopropyl, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, aminomethyl,1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino, N-ethylamino,methanesulfonamido, amidosulfonyl, N-methylamidosulfonyl,N,N-dimethylamidosulfonyl, hydroxymethyl, 1-hydroxyethyl,2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl,ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, fluoro, chloro, bromo, and cyano;

[0437] Y⁰ is selected from the group of formulas consisting of:

[0438]  R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, methyl, ethyl, isopropyl, propyl, carboxy,amidino, guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy,amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino,dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl,ethylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, andcyano;

[0439] R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no morethan one of R¹⁶ and R¹⁹ is Q^(b) the same time and that Q^(b) is Q^(be).

[0440] In a most preferred specific embodiment of Formula I, compoundshave the Formula I-EMPS wherein B is an aromatic:

[0441] (I-EMPS wherein B is aromatic)

[0442] or a pharmaceutically acceptable salt thereof, wherein;

[0443] B is selected from the group consisting of phenyl, 2-thienyl,3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, and5-isoxazolyl, wherein a carbon adjacent to the carbon at the point ofattachment is optionally substituted by R³², the other carbon adjacentto the carbon at the point of attachment is optionally substituted byR³⁶, a carbon adjacent to R³² and two atoms from the carbon at the pointof attachment is optionally substituted by R³³, a carbon adjacent to R³⁶and two atoms from the carbon at the point of attachment is optionallysubstituted by R³⁵, and any carbon adjacent to both R³³ and R³⁵ isoptionally substituted by R³⁴;

[0444] R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from thegroup consisting of hydrido, amidino, guanidino, methyl, ethyl, methoxy,ethoxy, hydroxy, amino, N-methylamino, dimethylamino, methylthio,ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl,hydroxymethyl, amidocarbonyl, carboxy, cyano, and Q^(b);

[0445] A is selected from the group consisting of single covalent bond,NH, N(CH₃), CH₂, CH₃CH, and CH₂CH₂;

[0446] Q^(b) is selected from the group consisting of NR²⁰R²¹ andC(NR²⁵)NR²³R²⁴, with the proviso that said Q^(b) group is bondeddirectly to a carbon atom;

[0447] R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from thegroup consisting of hydrido, methyl, and ethyl;

[0448] Q^(S) is CH₂.

[0449] In another most preferred specific embodiment of Formula I,compounds have the Formula I-EMPS wherein B is a non-cyclic substituent:

[0450] wherein B is a non-cyclic substituent)

[0451] or a pharmaceutically acceptable salt thereof, wherein;

[0452] B is selected from the group consisting of hydrido, ethyl,2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butenyl, 2-butynyl,sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl,3-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, 3-pentyl, 2-methylbutyl,2-methyl-2-butenyl, 3-methylbutyl, 3-methyl-2-butenyl, 1-hexyl,2-hexenyl, 3-hexenyl, 4-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl,2-hexyl, 1-methyl-2-pentenyl, 1-methyl -3-pentenyl, 1-methyl-2-pentynyl,1-methyl-3-pentynyl, 3-hexyl, 1-ethyl -2-butenyl, 1-heptyl, 2-heptenyl,3-heptenyl, 4-heptenyl, 5-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl,5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl -3-hexenyl,1-methyl-4-hexenyl, 1-methyl-2-hexynyl, 1-methyl-3-hexynyl,1-methyl-4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl,1-ethyl -2-pentynyl, 1-ethyl-3-pentynyl, 2,2,2-trifluoroethyl,2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl,4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and3,3,3-trifluoropropyl, wherein each member of group B is optionallysubstituted at any carbon up to and including 5 atoms from the point ofattachment of B to A with one or more of the group consisting of R³²,R³³, R³⁴, R³⁵, and R³⁶;

[0453] R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from thegroup consisting of hydrido, amidino, guanidino, methyl, ethyl, methoxy,ethoxy, hydroxy, amino, N-methylamino, dimethylamino, methylthio,ethylthio, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,fluoro, chloro, bromo, amidosulfonyl, N-methylamidosulfonyl,hydroxymethyl, amidocarbonyl, carboxy, cyano, and Q^(b);

[0454] A is selected from the group consisting of single covalent bond,NH, N(CH₃), CH₂, CH₃CH, and CH₂CH₂;

[0455] A is optionally selected from the group consisting of CH₂N(CH₃),CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), and CH₂CH₂N(CH₂CH₃) with the proviso that Bis hydrido;

[0456] Q^(b) is selected from the group consisting of NR²⁰R²¹,C(NR²⁵)NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the proviso that saidQ^(b) group is bonded directly to a carbon atom;

[0457] R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected fromthe group consisting of hydrido, methyl, and ethyl;

[0458] Q^(s) is CH₂.

[0459] In still another most preferred specific embodiment of Formula I,compounds have the Formula I-EMPS wherein B is a non-aromatic cyclicsubstituent:

[0460] (I-EMPS wherein B is a non-aromatic cyclic substituent)

[0461] or a pharmaceutically acceptable salt thereof, wherein;

[0462] B is optionally selected from the group consisting ofcyclopropyl, cyclobutyl, oxetan-3-yl, azetidin-3-yl, thiaetan-3-yl,cyclopentyl, cyclohexyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl,2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrothienyl, and3-tetrahydrothienyl, wherein each ring carbon is optionally substitutedwith R³³, ring carbons and a nitrogen adjacent to the carbon atom at thepoint of attachment are optionally substituted with R⁹ or R¹³, a ringcarbon or nitrogen adjacent to the R⁹ position and two atoms from thepoint of attachment is optionally substituted with R¹⁰, and a ringcarbon or nitrogen adjacent to the R¹³ position and two atoms from thepoint of attachment is optionally substituted with R¹²;

[0463] R³³ are independently selected from the group consisting ofhydrido, amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy,carboxy, amino, N-methylamino, dimethylamino, methylthio, ethylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro,bromo, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl,amidocarbonyl, cyano, and Q^(b);

[0464] A is selected from the group consisting of single covalent bond,NH, N(CH₃), CH₂, CH₃CH, and CH₂CH₂;

[0465] Q^(b) is selected from the group consisting of NR²⁰R²¹ andC(NR²⁵)NR²³R²⁴, with the proviso that said Q^(b) group is bondeddirectly to a carbon atom;

[0466] R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selected from thegroup consisting of hydrido, methyl, and ethyl;

[0467] Q^(s) is CH₂.

[0468] The most preferred specific embodiment (I-EMPS) compounds of thepresent invention having the Formula:

[0469] or a pharmaceutically acceptable salt thereof, have commonstructural units, wherein;

[0470] M is selected from the group consisting of N and R¹—C;

[0471] R¹ is selected from the group consisting of hydrido, hydroxy,amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl,trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio,trifluoromethoxy, fluoro, and chloro;

[0472] R² is Z⁰—Q;

[0473] Z⁰ is a covalent single bond;

[0474] Q is selected from the group consisting of phenyl, 2-thienyl,2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl,and 3-pyridyl, wherein a carbon adjacent to the carbon at the point ofattachment is optionally substituted by R⁹, the other carbon adjacent tothe carbon at the point of attachment is optionally substituted by R¹³,a carbon adjacent to R⁹ and two atoms from the carbon at the point ofattachment is optionally substituted by R¹⁰, a carbon adjacent to R¹³and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹², and any carbon adjacent to both R¹⁰ and R¹² isoptionally substituted by R¹¹;

[0475] R⁹, R¹¹, and R¹³ are independently selected from the groupconsisting of hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy, amino,N-methylamino, N,N-dimethylamino, methylthio, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,carboxy, and cyano;

[0476] R¹⁰ and R¹² are independently selected from the group consistingof hydrido, amidino, amidocarbonyl, N-methylamidocarbonyl, guanidino,methyl, ethyl, methoxy, ethoxy, hydroxy, hydroxymethyl, 1-hydroxyethyl,2-hydroxyethyl, carboxy, carboxymethyl, amino, acetamido,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,trifluoroacetamido, aminomethyl, N-methylamino, dimethylamino,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,methoxycarbonyl, fluoro, chloro, bromo, and cyano;

[0477] Y⁰ is selected from the group of formulas consisting of:

[0478]  R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selected from the groupconsisting of hydrido, methyl, ethyl, amidino, guanidino, methoxy,hydroxy, amino, aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino,dimethylamino, methylthio, ethylthio, trifluoromethylthio,methylsulfinyl, methylsulfonyl, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, trifluoromethoxy, fluoro, chloro, amidosulfonyl,N-methylamidosulfonyl, hydroxymethyl, carboxy, and cyano.

[0479] The compounds of this invention can be used in anticoagulanttherapy for the treatment and prevention of a variety of thromboticconditions including coronary artery and cerebrovascular disease. Thecompounds of this invention can be used to inhibit serine proteaseassociated with the coagulation cascade and factors II, VII, VIII, IX,X, XI, or XII. The compounds of the invention can inhibit the formationof blood platelet aggregates, inhibit the formation of fibrin, inhibitthrombus formation, and inhibiting embolus formation in a mammal, inblood, in blood products, and in mammalian organs. The compounds alsocan be used for treating or preventing unstable angina, refractoryangina, myocardial infarction, transient ischemic attacks, atrialfibrillation, thrombotic stroke, embolic stroke, deep vein thrombosis,disseminated intravascular coagulation, ocular build up of fibrin, andreocclusion or restenosis of recanalized vessels in a mammal. Thecompounds can also be used in prophylactic treatment of subjects who areat risk of developing such disorders. The compounds can be used to lowerthe risk of atherosclerosis. The compounds of Formula (I) would also beuseful in prevention of cerebral vascular accident (CVA) or stroke.

[0480] Besides being useful for human treatment, these compounds arealso useful for veterinary treatment of companion animals, exoticanimals and farm animals, including mammals, rodents, and the like. Morepreferred animals include horses, dogs, and cats.

[0481] In yet another embodiment of the present invention, the novelcompounds are selected from the compounds set forth in Examples 1through Example 7.

[0482] The use of generic terms in the description of the compounds areherein defined for clarity.

[0483] Standard single letter elemental symbols are used to representspecific types of atoms unless otherwise defined. The symbol “C”represents a carbon atom. The symbol “O” represents an oxygen atom. Thesymbol “N” represents a nitrogen atom. The symbol “P” represents aphosphorus atom. The symbol “S” represents a sulfur atom. The symbol “H”represents a hydrido atom. Double letter elemental symbols are used asdefined for the elements of the periodical table (i.e., Cl representschlorine, Se represents selenium, etc.).

[0484] As utilized herein, the term “alkyl”, either alone or withinother terms such as “haloalkyl” and “alkylthio”, means an acyclic alkylradical containing from 1 to about 10, preferably from 3 to about 8carbon atoms and more preferably 3 to about 6 carbon atoms. Said alkylradicals may be optionally substituted with groups as defined below.Examples of such radicals include methyl, ethyl, chloroethyl,hydroxyethyl, n-propyl, oxopropyl, isopropyl, n-butyl, cyanobutyl,isobutyl, sec-butyl, tert-butyl, pentyl, aminopentyl, iso-amyl, hexyl,octyl and the like.

[0485] The term “alkenyl” refers to an unsaturated, acyclic hydrocarbonradical in so much as it contains at least one double bond. Such alkenylradicals contain from about 2 to about 10 carbon atoms, preferably fromabout 3 to about 8 carbon atoms and more preferably 3 to about 6 carbonatoms. Said alkenyl radicals may be optionally substituted with groupsas defined below. Examples of suitable alkenyl radicals includepropenyl, 2-chloropropenyl, buten-1-yl, isobutenyl, penten-1-yl,2-2-methylbuten-1-yl, 3-methylbuten-1-yl, hexen-1-yl,3-hydroxyhexen-1-yl, hepten-1-yl, and octen-1-yl, and the like.

[0486] The term “alkynyl” refers to an unsaturated, acyclic hydrocarbonradical in so much as it contains one or more triple bonds, suchradicals containing about 2 to about 10 carbon atoms, preferably havingfrom about 3 to about 8 carbon atoms and more preferably having 3 toabout 6 carbon atoms. Said alkynyl radicals may be optionallysubstituted with groups as defined below. Examples of suitable alkynylradicals include ethynyl, propynyl, hydroxypropynyl, butyn-1-yl,butyn-2-yl, pentyn-1-yl, pentyn-2-yl, 4-methoxypentyn-2-yl,3-methylbutyn-1-yl, hexyn-1-yl, hexyn-2-yl, hexyn-3-yl,3,3-dimethylbutyn-1-yl radicals and the like.

[0487] The term “hydrido” denotes a single hydrogen atom (H). Thishydrido radical may be attached, for example, to an oxygen atom to forma “hydroxyl” radical, one hydrido radical may be attached to a carbonatom to form a “methine” radical —CH═, or two hydrido radicals may beattached to a carbon atom to form a “methylene” (—CH₂—) radical.

[0488] The term “carbon” radical denotes a carbon atom without anycovalent bonds and capable of forming four covalent bonds.

[0489] The term “cyano” radical denotes a carbon radical having three offour covalent bonds shared by a nitrogen atom.

[0490] The term “hydroxyalkyl” embraces radicals wherein any one or moreof the alkyl carbon atoms is substituted with a hydroxyl as definedabove. Specifically embraced are monohydroxyalkyl, dihydroxyalkyl andpolyhydroxyalkyl radicals.

[0491] The term “alkanoyl” embraces radicals wherein one or more of theterminal alkyl carbon atoms are substituted with one or more carbonylradicals as defined below. Specifically embraced are monocarbonylalkyland dicarbonylalkyl radicals. Examples of monocarbonylalkyl radicalsinclude formyl, acetyl, and pentanoyl. Examples of dicarbonylalkylradicals include oxalyl, malonyl, and succinyl.

[0492] The term “alkylene” radical denotes linear or branched radicalshaving from 1 to about 10 carbon atoms and having attachment points fortwo or more covalent bonds. Examples of such radicals are methylene,ethylene, methylethylene, and isopropylidene.

[0493] The term “alkenylene” radical denotes linear or branched radicalshaving from 2 to about 10 carbon atoms, at least one double bond, andhaving attachment points for two or more covalent bonds. Examples ofsuch radicals are 1,1-vinylidene (CH₂═C), 1,2-vinylidene (—CH═CH—), and1,4-butadienyl (—CH═CH—CH═CH—).

[0494] The term “halo” means halogens such as fluorine, chlorine,bromine or iodine atoms.

[0495] The term “haloalkyl” embraces radicals wherein any one or more ofthe alkyl carbon atoms is substituted with halo as defined above.Specifically embraced are monohaloalkyl, dihaloalkyl and polyhaloalkylradicals. A monohaloalkyl radical, for one example, may have either abromo, chloro or a fluoro atom within the radical. Dihalo radicals mayhave two or more of the same halo atoms or a combination of differenthalo radicals and polyhaloalkyl radicals may have more than two of thesame halo atoms or a combination of different halo radicals. Morepreferred haloalkyl radicals are “lower haloalkyl” radicals having oneto about six carbon atoms. Examples of such haloalkyl radicals includefluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl,dichloromethyl, trichloromethyl, trifluoroethyl, pentafluoroethyl,heptafluoropropyl, difluorochloromethyl, dichlorofluoromethyl,difluoroethyl, difluoropropyl, dichloroethyl and dichloropropyl.

[0496] The term “hydroxyhaloalkyl” embraces radicals wherein any one ormore of the haloalkyl carbon atoms is substituted with hydroxy asdefined above. Examples of “hydroxyhaloalkyl” radicals includehexafluorohydroxypropyl.

[0497] The term “haloalkylene radical” denotes alkylene radicals whereinany one or more of the alkylene carbon atoms is substituted with halo asdefined above. Dihalo alkylene radicals may have two or more of the samehalo atoms or a combination of different halo radicals andpolyhaloalkylene radicals may have more than two of the same halo atomsor a combination of different halo radicals. More preferred haloalkyleneradicals are “lower haloalkylene” radicals having one to about sixcarbon atoms. Examples of “haloalkylene” radicals includedifluoromethylene, tetrafluoroethylene, tetrachloroethylene, alkylsubstituted monofluoromethylene, and aryl substitutedtrifluoromethylene.

[0498] The term “haloalkenyl” denotes linear or branched radicals havingfrom 1 to about 10 carbon atoms and having one or more double bondswherein any one or more of the alkenyl carbon atoms is substituted withhalo as defined above. Dihaloalkenyl radicals may have two or more ofthe same halo atoms or a combination of different halo radicals andpolyhaloalkenyl radicals may have more than two of the same halo atomsor a combination of different halo radicals.

[0499] The terms “alkoxy” and “alkoxyalkyl” embrace linear or branchedoxy-containing radicals each having alkyl portions of one to about tencarbon atoms, such as methoxy radical. The term “alkoxyalkyl” alsoembraces alkyl radicals having one or more alkoxy radicals attached tothe alkyl radical, that is, to form monoalkoxyalkyl and dialkoxyalkylradicals. More preferred alkoxy radicals are “lower alkoxy” radicalshaving one to six carbon atoms. Examples of such radicals includemethoxy, ethoxy, propoxy, butoxy, isopropoxy and tert-butoxy alkyls. The“alkoxy” radicals may be further substituted with one or more haloatoms, such as fluoro, chloro or bromo, to provide “haloalkoxy” and“haloalkoxyalkyl” radicals. Examples of such haloalkoxy radicals includefluoromethoxy, chloromethoxy, trifluoromethoxy, difluoromethoxy,trifluoroethoxy, fluoroethoxy, tetrafluoroethoxy, pentafluoroethoxy, andfluoropropoxy. Examples of such haloalkoxyalkyl radicals includefluoromethoxymethyl, chloromethoxyethyl, trifluoromethoxymethyl,difluoromethoxyethyl, and trifluoroethoxymethyl.

[0500] The terms “alkenyloxy” and “alkenyloxyalkyl” embrace linear orbranched oxy-containing radicals each having alkenyl portions of two toabout ten carbon atoms, such as ethenyloxy or propenyloxy radical. Theterm “alkenyloxyalkyl” also embraces alkenyl radicals having one or morealkenyloxy radicals attached to the alkyl radical, that is, to formmonoalkenyloxyalkyl and dialkenyloxyalkyl radicals. More preferredalkenyloxy radicals are “lower alkenyloxy” radicals having two to sixcarbon atoms. Examples of such radicals include ethenyloxy, propenyloxy,butenyloxy, and isopropenyloxy alkyls. The “alkenyloxy” radicals may befurther substituted with one or more halo atoms, such as fluoro, chloroor bromo, to provide “haloalkenyloxy” radicals. Examples of suchradicals include trifluoroethenyloxy, fluoroethenyloxy,difluoroethenyhloxy, and fluoropropenyloxy.

[0501] The term “haloalkoxyalkyl” also embraces alkyl radicals havingone or more haloalkoxy radicals attached to the alkyl radical, that is,to form monohaloalkoxyalkyl and dihaloalkoxyalkyl radicals. The term“haloalkenyloxy” also embraces oxygen radicals having one or morehaloalkenyloxy radicals attached to the oxygen radical, that is, to formmonohaloalkenyloxy and dihaloalkenyloxy radicals. The term“haloalkenyloxyalkyl” also embraces alkyl radicals having one or morehaloalkenyloxy radicals attached to the alkyl radical, that is, to formmonohaloalkenyloxyalkyl and dihaloalkenyloxyalkyl radicals.

[0502] The term “alkylenedioxy” radicals denotes alkylene radicalshaving at least two oxygens bonded to a single alkylene group. Examplesof “alkylenedioxy” radicals include methylenedioxy, ethylenedioxy,alkylsubstituted methylenedioxy, and arylsubstituted methylenedioxy. Theterm “haloalkylenedioxy” radicals denotes haloalkylene radicals havingat least two oxy groups bonded to a single haloalkyl group. Examples of“haloalkylenedioxy” radicals include difluoromethylenedioxy,tetrafluoroethylenedioxy, tetrachloroethylenedioxy, alkylsubstitutedmonofluoromethylenedioxy, and arylsubstituted monofluoromethylenedioxy.

[0503] The term “aryl”, alone or in combination, means a carbocyclicaromatic system containing one, two or three rings wherein such ringsmay be attached together in a pendant manner or may be fused. The term“fused” means that a second ring is present (ie, attached or formed) byhaving two adjacent atoms in common (ie, shared) with the first ring.The term “fused” is equivalent to the term “condensed”. The term “aryl”embraces aromatic radicals such as phenyl, naphthyl, tetrahydronaphthyl,indane and biphenyl.

[0504] The term “perhaloaryl” embraces aromatic radicals such as phenyl,naphthyl, tetrahydronaphthyl, indane and biphenyl wherein the arylradical is substituted with 3 or more halo radicals as defined below.

[0505] The term “heterocyclyl” embraces saturated and partiallysaturated heteroatom-containing ring-shaped radicals having from 4through 15 ring members, herein referred to as “C4-C15 heterocyclyl”,selected from carbon, nitrogen, sulfur and oxygen, wherein at least onering atom is a heteroatom. Heterocyclyl radicals may contain one, two orthree rings wherein such rings may be attached in a pendant manner ormay be fused. Examples of saturated heterocyclic radicals includesaturated 3 to 6-membered heteromonocylic group containing 1 to 4nitrogen atoms[e.g. pyrrolidinyl, imidazolidinyl, piperidino,piperazinyl, etc.]; saturated 3 to 6-membered heteromonocyclic groupcontaining 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [e.g.morpholinyl, etc.]; saturated 3 to 6-membered heteromonocyclic groupcontaining 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms [e.g.,thiazolidinyl, etc.]. Examples of partially saturated heterocyclylradicals include dihydrothiophene, dihydropyran, dihydrofuran anddihydrothiazole. Non-limiting examples of heterocyclic radicals include2-pyrrolinyl, 3-pyrrolinyl, pyrrolindinyl, 1,3-dioxolanyl, 2H-pyranyl,4H-pyranyl, piperidinyl, 1,4-dioxanyl, morpholinyl, 1,4-dithianyl,thiomorpholinyl, and the like.

[0506] The term “heteroaryl” embraces fully unsaturatedheteroatom-containing ring-shaped aromatic radicals having from 5through 15 ring members selected from carbon, nitrogen, sulfur andoxygen, wherein at least one ring atom is a heteroatom. Heteroarylradicals may contain one, two or three rings wherein such rings may beattached in a pendant manner or may be fused. Examples of “heteroaryl”radicals, include unsaturated 5 to 6 membered heteromonocyclyl groupcontaining 1 to 4 nitrogen atoms, for example, pyrrolyl, pyrrolinyl,imidazolyl, pyrazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, pyrimidyl,pyrazinyl, pyridazinyl, triazolyl [e.g., 4H-1,2,4-triazolyl,1H-1,2,3-triazolyl, 2H-1,2,3-triazolyl, etc.] tetrazolyl [e.g.1H-tetrazolyl, 2H-tetrazolyl, etc.], etc.; unsaturated condensedheterocyclic group containing 1 to 5 nitrogen atoms, for example,indolyl, isoindolyl, indolizinyl, benzimidazolyl, quinolyl, isoquinolyl,indazolyl, benzotriazolyl, tetrazolopyridazinyl [e.g., tetrazolo[1,5-b]pyridazinyl, etc.], etc.; unsaturated 3 to 6-memberedheteromonocyclic group containing an oxygen atom, for example, pyranyl,2-furyl, 3-furyl, etc.; unsaturated 5 to 6-membered heteromonocyclicgroup containing a sulfur atom, for example, 2-thienyl, 3-thienyl, etc.;unsaturated 5- to 6-membered heteromonocyclic group containing 1 to 2oxygen atoms and 1 to 3 nitrogen atoms, for example, oxazolyl,isoxazolyl, oxadiazolyl [e.g., 1,2,4-oxadiazolyl, 1,3,4-oxadiazolyl,1,2,5-oxadiazolyl, etc.] etc.; unsaturated condensed heterocyclic groupcontaining 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [e.g.benzoxazolyl, benzoxadiazolyl, etc.]; unsaturated 5 to 6-memberedheteromonocyclic group containing 1 to 2 sulfur atoms and 1 to 3nitrogen atoms, for example, thiazolyl, thiadiazolyl [e.g.,1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,5-thiadiazolyl, etc.] etc.;unsaturated condensed heterocyclic group containing 1 to 2 sulfur atomsand 1 to 3 nitrogen atoms [e.g., benzothiazolyl, benzothiadiazolyl,etc.] and the like. The term also embraces radicals where heterocyclicradicals are fused with aryl radicals. Examples of such fused bicyclicradicals include benzofuran, benzothiophene, and the like. Said“heterocyclyl” group may have 1 to 3 substituents as defined below.Preferred heterocyclic radicals include five to twelve membered fused orunfused radicals. Non-limiting examples of heteroaryl radicals includepyrrolyl, pyridinyl, pyridyloxy, pyrazolyl, triazolyl, pyrimidinyl,pyridazinyl, oxazolyl, thiazolyl, imidazolyl, indolyl, thiophenyl,furanyl, tetrazolyl, 2-imidazolinyl, imidazolidinyl, 2-pyrazolinyl,pyrazolidinyl, isoxazolyl, isothiazolyl, 1,2,3-oxadiazolyl,1,2,3-triazolyl, 1,3,4-thiadiazolyl, pyrazinyl, piperazinyl,1,3,5-triazinyl, 1,3,5-trithianyl, benzo(b)thiophenyl, benzimidazoyl,quinolinyl, tetraazolyl, and the like.

[0507] The term “sulfonyl”, whether used alone or linked to other termssuch as alkylsulfonyl, denotes respectively divalent radicals —SO₂—.“Alkylsulfonyl”, embraces alkyl radicals attached to a sulfonyl radical,where alkyl is defined as above. “Alkylsulfonylalkyl”, embracesalkylsulfonyl radicals attached to an alkyl radical, where alkyl isdefined as above. “Haloalkylsulfonyl”, embraces haloalkyl radicalsattached to a sulfonyl radical, where haloalkyl is defined as above.“Haloalkylsulfonylalkyl”, embraces haloalkylsulfonyl radicals attachedto an alkyl radical, where alkyl is defined as above. The term“aminosulfonyl” denotes an amino radical attached to a sulfonyl radical.

[0508] The term “sulfinyl”, whether used alone or linked to other termssuch as alkylsulfinyl, denotes respectively divalent radicals —S(O)—.“Alkylsulfinyl”, embraces alkyl radicals attached to a sulfinyl radical,where alkyl is defined as above. “Alkylsulfinylalkyl”, embracesalkylsulfinyl radicals attached to an alkyl radical, where alkyl isdefined as above. “Haloalkylsulfinyl”, embraces haloalkyl radicalsattached to a sulfinyl radical, where haloalkyl is defined as above.“Haloalkylsulfinylalkyl”, embraces haloalkylsulfinyl radicals attachedto an alkyl radical, where alkyl is defined as above.

[0509] The term “aralkyl” embraces aryl-substituted alkyl radicals.Preferable aralkyl radicals are “lower aralkyl” radicals having arylradicals attached to alkyl radicals having one to six carbon atoms.Examples of such radicals include benzyl, diphenylmethyl,triphenylmethyl, phenylethyl and diphenylethyl. The terms benzyl andphenylmethyl are interchangeable.

[0510] The term “heteroaralkyl” embraces heteroaryl-substituted alkylradicals wherein the heteroaralkyl radical may be additionallysubstituted with three or more substituents as defined above for aralkylradicals. The term “perhaloaralkyl” embraces aryl-substituted alkylradicals wherein the aralkyl radical is substituted with three or morehalo radicals as defined above.

[0511] The term “aralkylsulfinyl”, embraces aralkyl radicals attached toa sulfinyl radical, where aralkyl is defined as above.“Aralkylsulfinylalkyl”, embraces aralkylsulfinyl radicals attached to analkyl radical, where alkyl is defined as above.

[0512] The term “aralkylsulfonyl”, embraces aralkyl radicals attached toa sulfonyl radical, where aralkyl is defined as above.“Aralkylsulfonylalkyl”, embraces aralkylsulfonyl radicals attached to analkyl radical, where alkyl is defined as above.

[0513] The term “cycloalkyl” embraces radicals having three to 15 carbonatoms. More preferred cycloalkyl radicals are “lower cycloalkyl”radicals having three to seven carbon atoms. Examples include radicalssuch as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl andcycloheptyl. The term cycloalkyl embraces radicals having seven to 15carbon atoms and having two to four rings. Examples include radicalssuch as norbornyl (i.e., bicyclo[2.2.1]heptyl) and adamantyl. The term“cycloalkylalkyl” embraces cycloalkyl-substituted alkyl radicals.Preferable cycloalkylalkyl radicals are “lower cycloalkylalkyl” radicalshaving cycloalkyl radicals attached to alkyl radicals having one to sixcarbon atoms. Examples of such radicals include cyclohexylhexyl. Theterm “cycloalkenyl” embraces radicals having three to ten carbon atomsand one or more carbon-carbon double bonds. Preferred cycloalkenylradicals are “lower cycloalkenyl” radicals having three to seven carbonatoms. Examples include radicals such as cyclobutenyl, cyclopentenyl,cyclohexenyl and cycloheptenyl. The term “halocycloalkyl” embracesradicals wherein any one or more of the cycloalkyl carbon atoms issubstituted with halo as defined above. Specifically embraced aremonohalocycloalkyl, dihalocycloalkyl and polyhalocycloalkyl radicals. Amonohalocycloalkyl radical, for one example, may have either a bromo,chloro or a fluoro atom within the radical. Dihalo radicals may have twoor more of the same halo atoms or a combination of different haloradicals and polyhalocycloalkyl radicals may have more than two of thesame halo atoms or a combination of different halo radicals. Morepreferred halocycloalkyl radicals are “lower halocycloalkyl” radicalshaving three to about eight carbon atoms. Examples of suchhalocycloalkyl radicals include fluorocyclopropyl, difluorocyclobutyl,trifluorocyclopentyl, tetrafluorocyclohexyl, and dichlorocyclopropyl.The term “halocycloalkenyl” embraces radicals wherein any one or more ofthe cycloalkenyl carbon atoms is substituted with halo as defined above.Specifically embraced are monohalocycloalkenyl, dihalocycloalkenyl andpolyhalocycloalkenyl radicals.

[0514] The term “cycloalkoxy” embraces cycloalkyl radicals attached toan oxy radical. Examples of such radicals includes cyclohexoxy andcyclopentoxy. The term “cycloalkoxyalkyl” also embraces alkyl radicalshaving one or more cycloalkoxy radicals attached to the alkyl radical,that is, to form monocycloalkoxyalkyl and dicycloalkoxyalkyl radicals.Examples of such radicals include cyclohexoxyethyl. The “cycloalkoxy”radicals may be further substituted with one or more halo atoms, such asfluoro, chloro or bromo, to provide “halocycloalkoxy” and“halocycloalkoxyalkyl” radicals.

[0515] The term “cycloalkylalkoxy” embraces cycloalkyl radicals attachedto an alkoxy radical. Examples of such radicals includescyclohexylmethoxy and cyclopentylmethoxy.

[0516] The term “cycloalkenyloxy” embraces cycloalkenyl radicalsattached to an oxy radical. Examples of such radicals includescyclohexenyloxy and cyclopentenyloxy. The term “cycloalkenyloxyalkyl”also embraces alkyl radicals having one or more cycloalkenyloxy radicalsattached to the alkyl radical, that is, to form monocycloalkenyloxyalkyland dicycloalkenyloxyalkyl radicals. Examples of such radicals includecyclohexenyloxyethyl. The “cycloalkenyloxy” radicals may be furthersubstituted with one or more halo atoms, such as fluoro, chloro orbromo, to provide “halocycloalkenyloxy” and “halocycloalkenyloxyalkyl”radicals.

[0517] The term “cycloalkylenedioxy” radicals denotes cycloalkyleneradicals having at least two oxygens bonded to a single cycloalkylenegroup. Examples of “alkylenedioxy” radicals include1,2-dioxycyclohexylene.

[0518] The term “cycloalkylsulfinyl”, embraces cycloalkyl radicalsattached to a sulfinyl radical, where cycloalkyl is defined as above.“Cycloalkylsulfinylalkyl”, embraces cycloalkylsulfinyl radicals attachedto an alkyl radical, where alkyl is defined as above. The term“Cycloalkylsulfonyl”, embraces cycloalkyl radicals attached to asulfonyl radical, where cycloalkyl is defined as above.“Cycloalkylsulfonylalkyl”, embraces cycloalkylsulfonyl radicals attachedto an alkyl radical, where alkyl is defined as above.

[0519] The term “cycloalkylalkanoyl” embraces radicals wherein one ormore of the cycloalkyl carbon atoms are substituted with one or morecarbonyl radicals as defined below. Specifically embraced aremonocarbonylcycloalkyl and dicarbonylcycloalkyl radicals. Examples ofmonocarbonylcycloalkyl radicals include cyclohexylcarbonyl,cyclohexylacetyl, and cyclopentylcarbonyl. Examples ofdicarbonylcycloalkyl radicals include 1,2-dicarbonylcyclohexane.

[0520] The term “alkylthio” embraces radicals containing a linear orbranched alkyl radical, of one to ten carbon atoms, attached to adivalent sulfur atom. More preferred alkylthio radicals are “loweralkylthio” radicals having one to six carbon atoms. An example of “loweralkylthio” is methylthio (CH₃—S—). The “alkylthio” radicals may befurther substituted with one or more halo atoms, such as fluoro, chloroor bromo, to provide “haloalkylthio” radicals. Examples of such radicalsinclude fluoromethylthio, chloromethylthio, trifluoromethylthio,difluoromethylthio, trifluoroethylthio, fluoroethylthio,tetrafluoroethylthio, pentafluoroethylthio, and fluoropropylthio.

[0521] The term “alkyl aryl amino” embraces radicals containing a linearor branched alkyl radical, of one to ten carbon atoms, and one arylradical both attached to an amino radical. Examples includeN-methyl-4-methoxyaniline, N-ethyl-4-methoxyaniline, andN-methyl-4-trifluoromethoxyaniline.

[0522] The terms alkylamino denotes “monoalkylamino” and “dialkylamino”containing one or two alkyl radicals, respectively, attached to an aminoradical.

[0523] The terms arylamino denotes “monoarylamino” and “diarylamino”containing one or two aryl radicals, respectively, attached to an aminoradical. Examples of such radicals include N-phenylamino andN-naphthylamino.

[0524] The term “aralkylamino”, embraces aralkyl radicals attached to anamino radical, where aralkyl is defined as above. The term aralkylaminodenotes “monoarakylamino” and “diaralkylamino” containing one or twoaralkyl radicals, respectively, attached to an amino radical. The termaralkylamino further denotes “monoaralkyl monoalkylamino” containing onearalkyl radical and one alkyl radical attached to an amino radical.

[0525] The term “arylsulfinyl” embraces radicals containing an arylradical, as defined above, attached to a divalent S(O) atom. The term“arylsulfinylalkyl” denotes arylsulfinyl radicals attached to a linearor branched alkyl radical, of one to ten carbon atoms.

[0526] The term “arylsulfonyl”, embraces aryl radicals attached to asulfonyl radical, where aryl is defined as above. “arylsulfonylalkyl”,embraces arylsulfonyl radicals attached to an alkyl radical, where alkylis defined as above. The term “heteroarylsulfinyl” embraces radicalscontaining an heteroaryl radical, as defined above, attached to adivalent S(O) atom. The term “heteroarylsulfinylalkyl” denotesheteroarylsulfinyl radicals attached to a linear or branched alkylradical, of one to ten carbon atoms. The term “Heteroarylsulfonyl”,embraces heteroaryl radicals attached to a sulfonyl radical, whereheteroaryl is defined as above. “Heteroarylsulfonylalkyl”, embracesheteroarylsulfonyl radicals attached to an alkyl radical, where alkyl isdefined as above.

[0527] The term “aryloxy” embraces aryl radicals, as defined above,attached to an oxygen atom. Examples of such radicals include phenoxy,4-chloro-3-ethylphenoxy, 4-chloro-3-methylphenoxy,3-chloro4-ethylphenoxy, 3,4-dichlorophenoxy, 4methylphenoxy,3-trifluoromethoxyphenoxy, 3-trifluoromethylphenoxy, 4-fluorophenoxy,3,4dimethylphenoxy, 5-bromo-2-fluorophenoxy, 4-bromo-3-fluorophenoxy,4-fluoro-3-methylphenoxy, 5,6,7,8-tetrahydronaphthyloxy,3-isopropylphenoxy, 3-cyclopropylphenoxy, 3-ethylphenoxy,3-pentafluoroethylphenoxy, 3-(1,1,2,2-tetrafluoroethoxy)-phenoxy, and4-tert -butylphenoxy.

[0528] The term “aroyl” embraces aryl radicals, as defined above,attached to an carbonyl radical as defined above. Examples of suchradicals include benzoyl and toluoyl.

[0529] The term “aralkanoyl” embraces aralkyl radicals, as definedherein, attached to an carbonyl radical as defined above. Examples ofsuch radicals include, for example, phenylacetyl.

[0530] The term “aralkoxy” embraces oxy-containing aralkyl radicalsattached through an oxygen atom to other radicals. More preferredaralkoxy radicals are “lower aralkoxy” radicals having phenyl radicalsattached to lower alkoxy radical as described above. Examples of suchradicals include benzyloxy, 1-phenylethoxy, 3-trifluoromethoxybenzyloxy,3-trifluoromethylbenzyloxy, 3,5-difluorobenyloxy, 3-bromobenzyloxy,4-propylbenzyloxy, 2-fluoro-3-trifluoromethylbenzyloxy, and2-phenylethoxy.

[0531] The term “aryloxyalkyl” embraces aryloxy radicals, as definedabove, attached to an alkyl group. Examples of such radicals includephenoxymethyl.

[0532] The term “haloaryloxyalkyl” embraces aryloxyalkyl radicals, asdefined above, wherein one to five halo radicals are attached to anaryloxy group.

[0533] The term “heteroaroyl” embraces heteroaryl radicals, as definedabove, attached to an carbonyl radical as defined above. Examples ofsuch radicals include furoyl and nicotinyl.

[0534] The term “heteroaralkanoyl” embraces heteroaralkyl radicals, asdefined herein, attached to an carbonyl radical as defined above.Examples of such radicals include, for example, pyridylacetyl andfurylbutyryl.

[0535] The term “heteroaralkoxy” embraces oxy-containing heteroaralkylradicals attached through an oxygen atom to other radicals. Morepreferred heteroaralkoxy radicals are “lower heteroaralkoxy” radicalshaving heteroaryl radicals attached to lower alkoxy radical as describedabove.

[0536] The term “haloheteroaryloxyalkyl” embraces heteroaryloxyalkylradicals, as defined above, wherein one to four halo radicals areattached to an heteroaryloxy group.

[0537] The term “heteroarylamino” embraces heterocyclyl radicals, asdefined above, attached to an amino group. Examples of such radicalsinclude pyridylamino.

[0538] The term “heteroarylaminoalkyl” embraces heteroarylaminoradicals, as defined above, attached to an alkyl group. Examples of suchradicals include pyridylmethylamino.

[0539] The term “heteroaryloxy” embraces heterocyclyl radicals, asdefined above, attached to an oxy group. Examples of such radicalsinclude 2-thiophenyloxy, 2-pyrimidyloxy, 2-pyridyloxy, 3-pyridyloxy, and4-pyridyloxy.

[0540] The term “heteroaryloxyalkyl” embraces heteroaryloxy radicals, asdefined above, attached to an alkyl group. Examples of such radicalsinclude 2-pyridyloxymethyl, 3-pyridyloxyethyl, and 4-pyridyloxymethyl.

[0541] The term “arylthio” embraces aryl radicals, as defined above,attached to an sulfur atom. Examples of such radicals includephenylthio.

[0542] The term “arylthioalkyl” embraces arylthio radicals, as definedabove, attached to an alkyl group. Examples of such radicals includephenylthiomethyl.

[0543] The term “alkylthioalkyl” embraces alkylthio radicals, as definedabove, attached to an alkyl group. Examples of such radicals includemethylthiomethyl. The term “alkoxyalkyl” embraces alkoxy radicals, asdefined above, attached to an alkyl group. Examples of such radicalsinclude methoxymethyl.

[0544] The term “carbonyl” denotes a carbon radical having two of thefour covalent bonds shared with an oxygen atom. The term “carboxy”embraces a hydroxyl radical, as defined above, attached to one of twounshared bonds in a carbonyl group. The term “carboxamide” embracesamino, monoalkylamino, dialkylamino, monocycloalkylamino,alkylcycloalkylamino, and dicycloalkylamino radicals, attached to one oftwo unshared bonds in a carbonyl group. The term “carboxamidoalkyl”embraces carboxamide radicals, as defined above, attached to an alkylgroup. The term “carboxyalkyl” embraces a carboxy radical, as definedabove, attached to an alkyl group. The term “carboalkoxy” embracesalkoxy radicals, as defined above, attached to one of two unshared bondsin a carbonyl group. The term “carboaralkoxy” embraces aralkoxyradicals, as defined above, attached to one of two unshared bonds in acarbonyl group. The term “monocarboalkoxyalkyl” embraces one carboalkoxyradical, as defined above, attached to an alkyl group. The term“dicarboalkoxyalkyl” embraces two carboalkoxy radicals, as definedabove, attached to an alkylene group. The term “monocyanoalkyl” embracesone cyano radical, as defined above, attached to an alkyl group. Theterm “dicyanoalkylene” embraces two cyano radicals, as defined above,attached to an alkyl group. The term “carboalkoxycyanoalkyl” embracesone cyano radical, as defined above, attached to an carboalkoxyalkylgroup.

[0545] The term “acyl”, alone or in combination, means a carbonyl orthionocarbonyl group bonded to a radical selected from, for example,hydrido, alkyl, alkenyl, alkynyl, haloalkyl, alkoxy, alkoxyalkyl,haloalkoxy, aryl, heterocyclyl, heteroaryl, alkylsulfinylalkyl,alkylsulfonylalkyl, aralkyl, cycloalkyl, cycloalkylalkyl, cycloalkenyl,alkylthio, arylthio, amino, alkylamino, dialkylamino, aralkoxy,arylthio, and alkylthioalkyl. Examples of “acyl” are formyl, acetyl,benzoyl, trifluoroacetyl, phthaloyl, malonyl, nicotinyl, and the like.The term “haloalkanoyl” embraces one or more halo radicals, as definedherein, attached to an alkanoyl radical as defined above. Examples ofsuch radicals include, for example, chloroacetyl, trifluoroacetyl,bromopropanoyl, and heptafluorobutanoyl.

[0546] The term “phosphono” embraces a pentavalent phosphorus attachedwith two covalent bonds to an oxygen radical. The term“dialkoxyphosphono” denotes two alkoxy radicals, as defined above,attached to a phosphono radical with two covalent bonds. The term“diaralkoxyphosphono” denotes two aralkoxy radicals, as defined above,attached to a phosphono radical with two covalent bonds. The term“dialkoxyphosphonoalkyl” denotes dialkoxyphosphono radicals, as definedabove, attached to an alkyl radical. The term “diaralkoxyphosphonoalkyl”denotes diaralkoxyphosphono radicals, as defined above, attached to analkyl radical.

[0547] The term “amino” denotes a nitrogen atom containing twosubstituents such as hydrido, hydroxy or alkyl and having one covalentbond available for bonding to a single atom such as carbon. Examples ofsuch amino radicals include, for example, —NH₂, —NHCH₃, —NHOH, and—NHOCH₃. The term “imino” denotes a nitrogen atom containing onesubstituent such as hydrido, hydroxy or alkyl and having two covalentbonds available for bonding to a single atom such as carbon. Examples ofsuch imino radicals include, for example, ═NH, ═NCH₃, ═NOH, and ═NOCH₃.The term “imino carbonyl” denotes a carbon radical having two of thefour covalent bond sites shared with an imino group. Examples of suchimino carbonyl radicals include, for example, C═NH, C═NCH₃, C═NOH, andC═NOCH₃. The term “amidino” embraces a substituted or unsubstitutedamino group bonded to one of two available bonds of an iminocarbonylradical. Examples of such amidino radicals include, for example,NH₂—C═NH, NH₂—C═NCH₃, NH₂—C═NOCH₃ and CH₃NH—C═NOH. The term “guanidino”denotes an amidino group bonded to an amino group as defined above wheresaid amino group can be bonded to a third group. Examples of suchguanidino radicals include, for example, NH₂—C(NH)—NH—, NH₂—C(NCH₃)—NH—,NH₂—C(NOCH₃)—NH—, and CH₃NH—C(NOH)—NH—.

[0548] The term “sulfonium” denotes a positively charged trivalentsulfur atom where said sulfur is substituted with three carbon basedgroups such as alkyl, alkenyl, aralkyl, or aryl. The term “dialkylsulfonium” denotes a sulfonium group where said sulfur is substitutedwith two alkyl groups. Examples of such dialkylsulfonium radicalsinclude, for example, (CH₃)₂S⁺—. The term “dialkyl sulfonium alkyl”denotes a dialkyl sulfonium group where said group is bonded to one bondof an alkylene group as defined above. Examples of suchdialkylsulfoniumalkyl radicals include (CH₃)₂S⁺—CH₂CH₂—.

[0549] The term “phosphonium” denotes a positively charged tetravalentphosphorus atom where said phosphorus is substituted with four carbonbased groups such as alkyl, alkenyl, aralkyl, or aryl. The term“trialkyl phosphonium” denotes a phosphonium group where said phosphorusis substituted with three alkyl groups. Examples of suchtrialkylphosphonium radicals include, for example, (CH₃)₃P⁺.

[0550] Said “alkyl”, “alkenyl”, “alkynyl”, “alkanoyl”, “alkylene”,“alkenylene”, “hydroxyalkyl”, “haloalkyl”, “haloalkylene”,“haloalkenyl”, “alkoxy”, “alkenyloxy”, “alkenyloxyalkyl”, “alkoxyalkyl”,“aryl”, “perhaloaryl”, “haloalkoxy”, “haloalkoxyalkyl”,“haloalkenyloxy”, “haloalkenyloxyalkyl”, “alkylenedioxy”,“haloalkylenedioxy”, “heterocyclyl”, “heteroaryl”, “hydroxyhaloalkyl”,“alkylsulfonyl”, “haloalkylsulfonyl”, “alkylsulfonylalkyl”,“haloalkylsulfonylalkyl”, “alkylsulfinyl”, “alkylsulfinylalkyl”,“haloalkylsulfinylalkyl”, “aralkyl”, “heteroaralkyl”, “perhaloaralkyl”,“aralkylsulfonyl”, “aralkylsulfonylalkyl”, “aralkylsulfinyl”,“aralkylsulfinylalkyl”, “cycloalkyl”, “cycloalkylalkanoyl”,“cycloalkylalkyl”, “cycloalkenyl”, “halocycloalkyl”, “halocycloalkenyl”,“cycloalkylsulfinyl”, “cycloalkylsulfinylalkyl”, “cycloalkylsulfonyl”,“cycloalkylsulfonylalkyl”, “cycloalkoxy”, “cycloalkoxyalkyl”,“cycloalkylalkoxy”, “cycloalkenyloxy”, “cycloalkenyloxyalkyl”,“cycloalkylenedioxy”, “halocycloalkoxy”, “halocycloalkoxyalkyl”,“halocycloalkenyloxy”, “halocycloalkenyloxyalkyl”, “alkylthio”,“haloalkylthio”, “alkylsulfinyl”, “amino”, “oxy”, “thio”, “alkylamino”,“arylamino”, “aralkylamino”, “arylsulfinyl”, “arylsulfinylalkyl”,“arylsulfonyl”, “arylsulfonylalkyl”, “heteroarylsulfinyl”,“heteroarylsulfinylalkyl”, “heteroarylsulfonyl”,“heteroarylsulfonylalkyl”, “heteroarylamino”, “heteroarylaminoalkyl”,“heteroaryloxy”, “heteroaryloxylalkyl”, “aryloxy”, “aroyl”,“aralkanoyl”, “aralkoxy”, “aryloxyalkyl”, “haloaryloxyalkyl”,“heteroaroyl”, “heteroaralkanoyl”, “heteroaralkoxy”,“heteroaralkoxyalkyl”, “arylthio”, “arylthioalkyl”, “alkoxyalkyl”,“acyl”, “amidino”, “guanidino”, “dialkylsulfonium”,“trialkylphosphonium”, and “dialkylsulfoniumalkyl” groups defined abovemay optionally have 1 or more non-hydrido substituents such as amidino,guanidino, dialkylsulfonium, trialkylphosphonium, dialkylsulfoniumalkyl,perhaloaralkyl, aralkylsulfonyl, aralkylsulfonylalkyl, aralkylsulfinyl,aralkylsulfinylalkyl, halocycloalkyl, halocycloalkenyl,cycloalkylsulfinyl, cycloalkylsulfinylalkyl, cycloalkylsulfonyl,cycloalkylsulfonylalkyl, heteroarylamino,N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl, heteroaryloxy,heteroaryloxylalkyl, haloalkylthio, alkanoyloxy, alkoxy, alkoxyalkyl,haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy, cycloalkenyloxy,cycloalkoxyalkyl, cycloalkylalkoxy, cycloalkenyloxyalkyl,cycloalkylenedioxy, halocycloalkoxy, halocycloalkoxyalkyl,halocycloalkenyloxy, halocycloalkenyloxyalkyl, hydroxy, amino, thio,nitro, lower alkylamino, alkylthio, alkylthioalkyl, arylamino,aralkylamino, arylthio, arylthioalkyl, heteroaralkoxyalkyl,alkylsulfinyl, alkylsulfinylalkyl, arylsulfinylalkyl, arylsulfonylalkyl,heteroarylsulfinylalkyl, heteroarylsulfonylalkyl, alkylsulfonyl,alkylsulfonylalkyl, haloalkylsulfinylalkyl, haloalkylsulfonylalkyl,alkylsulfonamido, alkylaminosulfonyl, amidosulfonyl, monoalkylamidosulfonyl, dialkyl amidosulfonyl, monoarylamidosulfonyl,arylsulfonamido, diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl,arylsulfinyl, arylsulfonyl, heteroarylthio, heteroarylsulfinyl,heteroarylsulfonyl, alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl,heteroaralkanoyl, haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy,alkenyloxyalkyl, alkylenedioxy, haloalkylenedioxy, cycloalkyl,cycloalkylalkanoyl, cycloalkenyl, lower cycloalkylalkyl, lowercycloalkenylalkyl, halo, haloalkyl, haloalkenyl, haloalkoxy,hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, aminoalkyl,hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy,aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl,heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl,heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl,carboalkoxy, alkoxycarbonyl, carboaralkoxy, carboxamido,carboxamidoalkyl, cyano, carbohaloalkoxy, phosphono, phosphonoalkyl,diaralkoxyphosphono, and diaralkoxyphosphonoalkyl.

[0551] The term “spacer” can include a covalent bond and a linear moietyhaving a backbone of 1 to 7 contiguous atoms. The spacer may have 1 to 7atoms of a univalent or multi-valent chain. Univalent chains may beconstituted by a radical selected from ═C(H)—, ═C(R^(2a))—, —O—, —S—,—S(O)—, —S(O)₂—, —NH—, —N(R^(2a))—, —N═, —CH(OH)—, ═C(OH)—,—CH(OR^(2a))—, ═C(OR^(2a))—, and —C(O)— wherein R^(2a) is selected fromalkyl, alkenyl, alkynyl, aryl, heteroaryl, aralkyl, aryloxyalkyl,alkoxyalkyl, alkylthioalkyl, arylthioalkyl, cycloalkyl, cycloalkylalkyl,haloalkyl, haloalkenyl, haloalkoxyalkyl, perhaloaralkyl,heteroarylalkyl, heteroaryloxyalkyl, heteroarylthioalkyl, andheteroarylalkenyl. Multi-valent chains may consist of a straight chainof 1 or 2 or 3 or 4 or 5 or 6 or 7 atoms or a straight chain of 1 or 2or 3 or 4 or 5 or 6 atoms with a side chain. The chain may beconstituted of one or more radicals selected from: lower alkylene, loweralkenyl, —O—, —O—CH₂—, —S—CH₂—, —CH₂CH₂—, ethenyl, —CH═CH(OH)—, —OCH₂O—,—O(CH₂)₂O—, —NHCH₂—, —OCH(R^(2a))O—, —O(CH₂CHR^(2a))O—, —OCF₂O—,—O(CF₂)₂O—, —S—, —S(O)—, —S(O)₂—, —N(H)—, —N(H)O—, —N(R^(2a))O—,—N(R^(2a))—, —C(O)—, —C(O)NH—, —C(O)NR^(2a)—, —N═, —OCH₂—, —SCH₂—,S(O)CH₂—, —CH₂C(O)—, —CH(OH)—, ═C(OH)—, —CH(OR^(2a))—, ═C(OR^(2a))—,S(O)₂CH₂—, and —NR^(2a)CH₂— and many other radicals defined above orgenerally known or ascertained by one of skill-in-the art. Side chainsmay include substituents such as 1 or more non-hydrido substituents suchas amidino, guanidino, dialkylsulfonium, trialkylphosphonium,dialkylsulfoniumalkyl, perhaloaralkyl, aralkylsulfonyl,aralkylsulfonylalkyl, aralkylsulfinyl, aralkylsulfinylalkyl,halocycloalkyl, halocycloalkenyl, cycloalkylsulfinyl,cycloalkylsulfinylalkyl, cycloalkylsulfonyl, cycloalkylsulfonylalkyl,heteroarylamino, N-heteroarylamino-N-alkylamino, heteroarylaminoalkyl,heteroaryloxy, heteroaryloxylalkyl, haloalkylthio, alkanoyloxy, alkoxy,alkoxyalkyl, haloalkoxylalkyl, heteroaralkoxy, cycloalkoxy,cycloalkenyloxy, cycloalkoxyalkyl, cycloalkylalkoxy,cycloalkenyloxyalkyl, cycloalkylenedioxy, halocycloalkoxy,halocycloalkoxyalkyl, halocycloalkenyloxy, halocycloalkenyloxyalkyl,hydroxy, amino, thio, nitro, lower alkylamino, alkylthio,alkylthioalkyl, arylamino, aralkylamino, arylthio, arylthioalkyl,heteroaralkoxyalkyl, alkylsulfinyl, alkylsulfinylalkyl,arylsulfinylalkyl, arylsulfonylalkyl, heteroarylsulfinylalkyl,heteroarylsulfonylalkyl, alkylsulfonyl, alkylsulfonylalkyl,haloalkylsulfinylalkyl, haloalkylsulfonylalkyl, alkylsulfonamido,alkylaminosulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, monoarylamidosulfonyl, arylsulfonamido,diarylamidosulfonyl, monoalkyl monoaryl amidosulfonyl, arylsulfinyl,arylsulfonyl, heteroarylthio, heteroarylsulfinyl, heteroarylsulfonyl,alkanoyl, alkenoyl, aroyl, heteroaroyl, aralkanoyl, heteroaralkanoyl,haloalkanoyl, alkyl, alkenyl, alkynyl, alkenyloxy, alkenyloxyalky,alkylenedioxy, haloalkylenedioxy, cycloalkyl, cycloalkenyl, lowercycloalkylalkyl, lower cycloalkenylalkyl, halo, haloalkyl, haloalkenyl,haloalkoxy, hydroxyhaloalkyl, hydroxyaralkyl, hydroxyalkyl, aminoalkyl,hydoxyheteroaralkyl, haloalkoxyalkyl, aryl, aralkyl, aryloxy, aralkoxy,aryloxyalkyl, saturated heterocyclyl, partially saturated heterocyclyl,heteroaryl, heteroaryloxy, heteroaryloxyalkyl, arylalkyl,heteroarylalkyl, arylalkenyl, heteroarylalkenyl, carboxyalkyl,carboalkoxy, carboaralkoxy, carboxamido, carboxamidoalkyl, cyano,carbohaloalkoxy, phosphono, phosphonoalkyl, diaralkoxyphosphono, anddiaralkoxyphosphonoalkyl.

[0552] Compounds of the present invention can exist in tautomeric,geometric or stereoisomeric forms. The present invention contemplatesall such compounds, including cis- and trans-geometric isomers, E- andZ-geometric isomers, R- and S-enantiomers, diastereomers, d-isomers,1-isomers, the racemic mixtures thereof and other mixtures thereof, asfalling within the scope of the invention. Pharmaceutically acceptablesales of such tautomeric, geometric or stereoisomeric forms are alsoincluded within the invention.

[0553] The terms “cis” and “trans” denote a form of geometric isomerismin which two carbon atoms connected by a double bond will each have ahydrogen atom on the same side of the double bond (“cis”) or on oppositesides of the double bond (“trans”).

[0554] Some of the compounds described contain alkenyl groups, and aremeant to include both cis and trans or “E” and “Z” geometric forms.

[0555] Some of the compounds described contain one or more stereocentersand are meant to include R, S, and mixtures of R and S forms for eachstereocenter present.

[0556] Some of the compounds described herein may contain one or moreketonic or aldehydic carbonyl groups or combinations thereof alone or aspart of a heterocyclic ring system. Such carbonyl groups may exist inpart or principally in the “keto” form and in part or principally as oneor more “enol” forms of each aldehyde and ketone group present.Compounds of the present invention having aldehydic or ketonic carbonylgroups are meant to include both “keto” and “enol” tautomeric forms.

[0557] Some of the compounds described herein may contain one or moreamide carbonyl groups or combinations thereof alone or as part of aheterocyclic ring system. Such carbonyl groups may exist in part orprincipally in the “keto” form and in part or principally as one or more“enol” forms of each amide group present. Compounds of the presentinvention having amidic carbonyl groups are meant to include both “keto”and “enol” tautomeric forms. Said amide carbonyl groups may be both oxo(C═O) and thiono (C═S) in type.

[0558] Some of the compounds described herein may contain one or moreimine or enamine groups or combinations thereof. Such groups may existin part or principally in the “imine” form and in part or principally asone or more “enamine” forms of each group present. Compounds of thepresent invention having said imine or enamine groups are meant toinclude both “imine” and “enamine” tautomeric forms.

[0559] The present invention also comprises a treatment and prophylaxisin anticoagulant therapy for the treatment and prevention of a varietyof thrombotic conditions including coronary artery and cerebrovasculardisease in a subject, comprising administering to the subject havingsuch disorder a therapeutically-effective amount of a compound ofFormula (I):

[0560] or a pharmaceutically-acceptable salt thereof.

[0561] As a further embodiment, compounds of the present invention ofFormula (I) or a pharmaceutically-acceptable salt thereof as definedabove, comprise a treatment and prophylaxis of coronary artery disease,cerebrovascular disease and other coagulation cascade related disordersin a subject, comprising administering to the subject having suchdisorder a therapeutically-effective amount of compounds of formula (I)of the present invention or a pharmaceutically-acceptable salt thereof.

[0562] Compounds of the present invention of Formula (I) or apharmaceutically-acceptable salt thereof can also be used wheneverinhibition of blood coagulation is required such as to preventcoagulation of stored whole blood and to prevent coagulation in otherbiological samples for testing or storage. Thus coagulation inhibitorsof the present inhibition can be added to or contacted with stored wholeblood and any medium containing or suspected of containing plasmacoagulation factors and in which it is desired that blood coagulation beinhibited, e.g. when contacting the mammal's blood with materialselected from the group consisting of vascular grafts, stents,orthopedic prothesis, cardiac prosthesis, and extracorporeal circulationsystems.

[0563] Compounds of Formula (I) are capable of inhibiting activity ofserine proteases related to the coagulation cascade, and thus could beused in the manufacture of a medicament, a method for the prophylacticor therapeutic treatment of diseases mediated by coagulation cascadeserine proteases, such as inhibiting the formation of blood plateletaggregates, inhibiting the formation of fibrin, inhibiting thrombusformation, and inhibiting embolus formation in a mammal, in blood, inblood products, and in mammalian organs. The compounds also can be usedfor treating or preventing unstable angina, refractory angina,myocardial infarction, transient ischemic attacks, atrial fibrillation,thrombotic stroke, embolic stroke, deep vein thrombosis, disseminatedintravascular coagulation, ocular build up of fibrin, and reocclusion orrestenosis of recanalized vessels in a mammal. The compounds also can beused to study the mechanism of action of coagulation cascade serineproteases to enable the design of better inhibitors and development ofbetter assay methods. The compounds of Formula (I) would be also usefulin prevention of cerebral vascular accident (CVA) or stroke.

[0564] Also included in the family of compounds of Formula (I) are thepharmaceutically-acceptable salts thereof. The term“pharmaceutically-acceptable salt” embraces salts commonly used to formalkali metal salts and to form addition salts of free acids or freebases. The nature of the salt is not critical, provided that it ispharmaceutically acceptable. Suitable pharmaceutically-acceptable acidaddition salts of compounds of Formula (I) may be prepared frominorganic acid or from an organic acid. Examples of such inorganic acidsare hydrochloric, hydrobromic, hydroiodic, nitric, carbonic, sulfuricand phosphoric acid. Appropriate organic acids may be selected fromaliphatic, cycloaliphatic, aromatic, araliphatic, heterocyclic,carboxylic and sulfonic classes of organic acids, examples of which areformic, acetic, propionic, succinic, glycolic, gluconic, lactic, malic,tartaric, citric, ascorbic, glucoronic, maleic, fumaric, pyruvic,aspartic, glutamic, benzoic, anthranilic, mesylic, salicylic,p-hydroxybenzoic, phenylacetic, mandelic, embonic (pamoic),methanesulfonic, ethylsulfonic, benzenesulfonic, sulfanilic, stearic,cyclohexylaminosulfonic, algenic, galacturonic acid. Suitablepharmaceutically-acceptable base addition salts of compounds of Formula(I) include metallic salts made from aluminum, calcium, lithium,magnesium, potassium, sodium and zinc or organic salts made fromN,N′-dibenzylethyleneldiamine, choline, chloroprocaine, diethanolamine,ethylenediamine, meglumine (N-methylglucamine) and procain. All of thesesalts may be prepared by conventional means from the correspondingcompound of Formula (I) by reacting, for example, the appropriate acidor base with the compound of Formula (I).

[0565] The present invention also comprises a pharmaceutical compositioncomprising a therapeutically-effective amount of a compound of Formulas(I) in association with at least one pharmaceutically-acceptablecarrier, adjuvant or diluent. Pharmaceutical compositions of the presentinvention can comprise the active compounds of Formula (I) inassociation with one or more non-toxic, pharmaceutically-acceptablecarriers and/or diluents and/or adjuvants (collectively referred toherein as “carrier” materials) and, if desired, other activeingredients. The active compounds of the present invention may beadministered by any suitable route, preferably in the form of apharmaceutical composition adapted to such a route, and in a doseeffective for the treatment intended.

[0566] The active compounds and composition may, for example, beadministered orally, intravascularly, intraperitoneally, subcutaneously,intramuscularly, oculary, or topically. For treating ocular build up offibrin, the compounds may be administered intraocularly or topically aswell as orally or parenterally.

[0567] The compounds can be administered in the form of a depotinjection or implant preparation which may be formulated in such amanner as to permit a sustained release of the active ingredient. Theactive ingredient can be compressed into pellets or small cylinders andimplanted subcutaneously or intramusculary as depot injections orimplants. Implants may employ inert materials such as biodegradablepolymers or synthetic silicones, for example, Silastic, silicone rubberor other silicon containing polymers.

[0568] The compounds can also be administered in the form of liposomedelivery systems, such as small unilamellar vesicles, large unilamellarvesicles and multilamellar vesicles. Liposomes can be formed from avariety of phospholipids, such as cholesterol, stearylamine orphosphatidylcholines.

[0569] The compounds may also be delivered by the use of monoclonalantibodies as individual carriers to which the compound molecules arecoupled. The compounds may also be coupled with soluble polymers astargetable drug carriers. Such polymers can includepolyvinylpyrrolidone, pyran copolymer,polyhydroxy-propylmethacrylamide-phenol,polyhydroxyethyl-aspartamide-phenol, or ployethyleneoxide-polylysinesubstituted with palmitoyl residues. Furthermore, the compounds may becoupled to a class of biodegradable polymers useful in achievingcontrolled release of a drug, for example, polylactic acid, polyglycolicacid, copolymers of polylactic and polyglycolic acid, polyepsiloncaprolactone, polyhydroxy butyric acid, polyorthoesters, polyacetals,polydihydropyrans, polycyanoacrylates and cross linked or amphitpathicblock copolymers of hydrogels.

[0570] For oral administration, the pharmaceutical composition may be inthe form of, for example, tablets, capsules (each of which includessustained release or timed release formulations), pills, powders,granules, elixers, tinctures, suspensions, liquids including syrups, andemulsions. The pharmaceutical composition is preferably made in the formof a dosage unit containing a particular amount of the activeingredient. Examples of such dosage units are tablets or capsules. Theactive ingredient may also be administered by injection as a compositionwherein, for example, saline, dextrose or water may be used as asuitable carrier.

[0571] The amount of therapeutically active compounds which areadministered and the dosage regimen for treating a disease conditionwith the compounds and/or compositions of this invention depends on avariety of factors, including the age, weight, sex and medical conditionof the subject, the severity of the disease, the route and frequency ofadministration, and the particular compound employed, and thus may varywidely.

[0572] The pharmaceutical compositions may contain active ingredients inthe range of about 0.1 to 2000 mg, and preferably in the range of about0.5 to 500 mg. A daily dose of about 0.01 to 100 mg/kg body weight, andpreferably between about 0.5 and about 20 mg/kg body weight, may beappropriate. The daily dose can be administered in one to four doses perday.

[0573] The compounds may be formulated in topical ointment or cream, oras a suppository, containing the active ingredients in a total amountof, for example, 0.075 to 30% w/w, preferably 0.2 to 20% w/w and mostpreferably 0.4 to 15% w/w. When formulated in an ointment, the activeingredients may be employed with either paraffinic or a water-miscibleointment base.

[0574] Alternatively, the active ingredients may be formulated in acream with an oil-in-water cream base. If desired, the aqueous phase ofthe cream base may include, for example at least 30% w/w of a polyhydricalcohol such as propylene glycol, butane-1,3-diol, mannitol, sorbitol,glycerol, polyethylene glycol and mixtures thereof. The topicalformulation may desirably include a compound which enhances absorptionor penetration of the active ingredient through the skin or otheraffected areas. Examples of such dermal penetration enhancers includedimethylsulfoxide and related analogs. The compounds of this inventioncan also be administered by a transdermal device. Preferably topicaladministration will be accomplished using a patch either of thereservoir and porous membrane type or of a solid matrix variety. Ineither case, the active agent is delivered continuously from thereservoir or microcapsules through a membrane into the active agentpermeable adhesive, which is in contact with the skin or mucosa of therecipient. If the active agent is absorbed through the skin, acontrolled and predetermined flow of the active agent is administered tothe recipient. In the case of microcapsules, the encapsulating agent mayalso function as the membrane.

[0575] The oily phase of the emulsions of this invention may beconstituted from known ingredients in a known manner. While the phasemay comprise merely an emulsifier, it may comprise a mixture of at leastone emulsifier with a fat or an oil or with both a fat and an oil.Preferably, a hydrophilic emulsifier is included together with alipophilic emulsifier which acts as a stabilizer. It is also preferredto include both an oil and a fat. Together, the emulsifier(s) with orwithout stabilizer(s) make-up the so-called emulsifying wax, and the waxtogether with the oil and fat make up the so-called emulsifying ointmentbase which forms the oily dispersed phase of the cream formulations.Emulsifiers and emulsion stabilizers suitable for use in the formulationof the present invention include Tween 60, Span 80, cetostearyl alcohol,myristyl alcohol, glyceryl monostearate, and sodium lauryl sulfate,among others.

[0576] The choice of suitable oils or fats for the formulation is basedon achieving the desired cosmetic properties, since the solubility ofthe active compound in most oils likely to be used in pharmaceuticalemulsion formulations is very low. Thus, the cream should preferably bea non-greasy, non-staining and washable product with suitableconsistency to avoid leakage from tubes or other containers. Straight orbranched chain, mono- or dibasic alkyl esters such as diisoadipate,isocetyl stearate, propylene glycol diester of coconut fatty acids,isopropyl myristate, decyl oleate, isopropyl palmitate, butyl stearate,2-ethylhexyl palmitate or a blend of branched chain esters may be used.These may be used alone or in combination depending on the propertiesrequired. Alternatively, high melting point lipids such as white softparaffin and/or liquid paraffin or other mineral oils can be used.

[0577] For therapeutic purposes, the active compounds of the presentinvention are ordinarily combined with one or more adjuvants appropriateto the indicated route of administration. If administered per os, thecompounds may be admixed with lactose, sucrose, starch powder, celluloseesters of alkanoic acids, cellulose alkyl esters, talc, stearic acid,magnesium stearate, magnesium oxide, sodium and calcium salts ofphosphoric and sulfuric acids, gelatin, acacia gum, sodium alginate,polyvinylpyrrolidone, and/or polyvinyl alcohol, and then tableted orencapsulated for convenient administration. Such capsules or tablets maycontain a controlled-release formulation as may be provided in adispersion of active compound in hydroxypropylmethyl cellulose.Formulations for parenteral administration may be in the form of aqueousor non-aqueous isotonic sterile injection solutions or suspensions.These solutions and suspensions may be prepared from sterile powders orgranules having one or more of the carriers or diluents mentioned foruse in the formulations for oral administration. The compounds may bedissolved in water, polyethylene glycol, propylene glycol, ethanol, cornoil, cottonseed oil, peanut oil, sesame oil, benzyl alcohol, sodiumchloride, and/or various buffers. Other adjuvants and modes ofadministration are well and widely known in the pharmaceutical art.

[0578] In practicing the methods of the present invention for thetreatment and prevention of a variety of thrombotic conditions includingcoronary artery and cerebrovascular disease, the compounds andpharmaceutical compositions of the present invention are administeredalone or in combination with one another, or in combination with othertherapeutics or in vivo diagnostic agents. The coagulation cascadeinhibitors of the present invention can also be co-administered withsuitable anti-platelet agreggation agents, including, but not limited toticlopidine or clopidrogel, fibrinogen receptor antagonists (e.g. totreat or prevent unstable angina or to prevent reocculsion afterangioplasty and restenosis), anti-coagulants such as aspirin, warfarinor heparins, thrombolytic agents such as plasminogen activators orstreptokinase to achieve synergistic effects in the treatment of variouspathologies, lipid lowering agents including antihypercholesterolemics(e.g. HMG CoA reductase inhibitors such as mevastatin, lovastatin,simvastatin, pravastatin, and fluvastatin, HMG CoA synthataseinhibitors, etc.), anti-diabetic drugs, or other cardiovascular agents(loop diuretics, thiazide type diuretics, nitrates, aldosteroneantagonistics (i.e., spironolactone and epoxymexlerenone), angiotensinconverting enzyme (e.g. ACE) inhibitors, angiotensin II receptorantagonists, beta-blockers, antiarrythmics, anti-hypertension agents,and calcium channel blockers) to treat or prevent atheriosclerosis. Forexample, patients suffering from coronary artery disease, and patientssubjected to angioplasty procedures, would benefit from coadministrationof fibrinogen receptor antagonists and coagulation cascade inhibitors ofthe present invention. Also, coagulation cascade inhibitors couldenhance the efficiency of tissue plasminogen activator-mediatedthrombolytic reperfusion.

[0579] Typical doses of coagulation cascade inhibitors of the presentinvention with other suitable anti-platelet agents, anticoagulationagents, cardiovascular therapeutic agents, or thrombolytic agents may bethe same as those doses of coagulation cascade inhibitors administeredwithout coadministration of additional anti-platelet agents,anticoagulation agents, cardiovascular therapeutic agents, orthrombolytic agents, or may be substantially less than those doses ofcoagulation cascade inhibitors administered without coadministration ofadditional anti-platelet agents, anticoagulation agents, cardiovasculartherapeutic agents, or thrombolytic agents, depending on a patient'stherapeutic needs.

[0580] All mentioned references are incorporated by reference as if herewritten.

[0581] Although this invention has been described with respect tospecific embodiments, the details of these embodiments are not to beconstrued as limitations. The following examples are provided toillustrate the present invention and are not intended to limit the scopethereof. Without further elaboration, it is believed that one skilled inthe art can, using the preceding descriptions, utilize the presentinvention to its fullest extent. Therefore the following preferredspecific embodiments are to be construed as merely illustrative and notlimitative of the remainder of the disclosure in any way whatsoever.Compounds containing multiple variations of the structural modificationsillustrated in the schemes or the following Examples are alsocontemplated. Those skilled in the art will readily understand thatknown variations of the conditions and processes of the followingpreparative procedures can be used to prepare these compounds.

[0582] One skilled in the art may use these generic methods to preparethe following specific examples, which have been or may be properlycharacterized by ¹H NMR, mass spectrometry, elemental composition, andsimilar procedures. These compounds also may be formed in vivo. Thefollowing examples contain detailed descriptions of the methods ofpreparation of compounds of Formula (I). These detailed descriptionsfall within the scope and are presented for illustrative purposes onlyand are not intended as a restriction on the scope of the invention. Allparts are by weight and temperatures are Degrees centigrade unlessotherwise indicated.

[0583] The following general synthetic sequences are useful in makingthe present invention. Abbreviations used in the schemes and tablesinclude: “AA” represents amino acids, “AcCN” represents acetonitrile,“AcOH” represents acetic acid, “BINAP” represents2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, “BnOH” represents benzylalcohol, “BnCHO” represents 2-phenylethanal, “BnSO₂Cl” representsbenzylsulfonyl chloride, “Boc” represents tert-butyloxycarbonyl, “BOP”represents benzotriazol-1-yl-oxy-tris-(dimethylamino), “bu” representsbutyl, “dba” represents dibenzylidene-acetone, “DCC” represents1,3-dicyclohexylcarbodiimide, “DCM” represents dichloromethane ormethylene chloride, “DIBAH” or “DIBAL” represents diisobutylaluminumhydride, “DMF” represents dimethylformamide, “DMSO” representsdimethylsulfoxide, “DPPA” represents diphenylphosphoryl azide”, “EDC”represents 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimidehydrochloride, “Ex. No.” represents Example Number, “Fmoc” represents9-fluorenylmethoxycarbonyl, “HOBt” represents hydroxybenzoltriazole”,“LDA” represents lithium diisopropylamide, “MW” represents molecularweight, “NMM” represents N-methylmorpholine, “Ph” represents phenyl oraryl, “PHTH” represents a phthaloyl group, “pnZ” represents4-nitrobenzyloxy-carbonyl, “PTC” represents a phase transfer catalyst ,“py” represents pyridine, “RNH₂” represents a primary organic amine,“SEM” represents 2-(trimethylsilyl)ethoxy-methyl chloride, “p-TsOH”represents paratoluenesulfonic acid, “TBAF” representstetrabutylammonium fluoride, “TBTU” represents2-(1H-benzotriozole-1-yl)-1,1,3,3-tetramethyl uronium tetrafluoroborate,“TEA” represents triethylamine, “TFA” represents trifluoroacetic acid,“THF” represents tetrahydrofuran, “TMS” represents trimethylsilyl,“TMSCN” represents trimethylsilyl cyanide, and “Cbz” or “Z” representsbenzyloxycarbonyl.

GENERAL SYNTHETIC PROCEDURES AND SPECIFIC EXAMPLES

[0584] The general synthetic approach to substituted uracils (i.e.,pyrimidinediones) is shown in Scheme 1 below. Several N-1 substitutedpyrimidinediones have been previously prepared, disclosed, and areuseful intermediates for the preparation of the compounds of thisinvention. Stirring a solution of such a N-1 substituted pyrimidinedioneand an α-haloacetate in dimethylsulfoxide, in the presence of potassiumcarbonate results in alkylation of the N-3 nitrogen. Reduction of thenitro functional group to the primary amine is easily accomplished withcatalytic palladium on carbon in an atmosphere of hydrogen. The primaryamine can then be reacted with a variety of raw materials including, butnot limited to, acid chlorides, acid anhydrides, sulfonyl chlorides,alkyl and aromatic halides, aldehydes, and ketones. The acetate estercan then be hydrolyzed to the acid with lithium hydroxide. The acid canthen be coupled with a wide range of desired amines under standardpeptide coupling conditions to give an amide. The amines used in theprocess of this invention are typically multi-functional and are reactedin protected form. Removal of these protecting groups provides thecompounds of the present invention.

[0585] This general uracil (i.e., pyrimidinedione) synthetic scheme isexemplified in Examples 1 and 2 below.

[0586] EX-1A) A solution of 1-benzyl-5-nitro-2,4(1H,3H) pyrimidinedione(6.14 g, 24.82 mmol) prepared as described by Vampa, G. and Pecorari P.Boll. Chim. Farm. 1987, 126,467-469 was dissolved in 100 mLdimethylsulfoxide and potassium dicarbonate (3.78 g, 27.34 mmol) wasadded in one portion with stirring. After approximately 10 minutes asolution of methyl bromoacetate (2.50 mL, 26.40 mmol) in 20 mLdimethylsulfoxide was added drop wise over a 10 minute period. Thereaction mixture was then heated to 40° C. and allowed to stir for 18hours. The reaction mixture was diluted with water (500 mL). The aqueoussolution was extracted with ethyl acetate (4×100 mL). The combinedorganic solutions were washed with water (1×150 mL), brine (2×150 mL).The organic solution was dried (MgSO₄), filtered, and concentrated togive an oil. The crude oil was purified by MPLC (20% ethylacetate/hexanes) to give pure1-Benzyl-3-methoxycarbonyl-methyl-5-nitro-2,4(1H,3H)pyrimidinedione(EX-1A) as a white solid in 81% yield: ¹H NMR (400 MHz, CDCl₃) δ 8.73(s, 1H) 7.38-7.30 (m, 5H), 5.06 (s, 2H), 4.69 (s, 2H), 3.72 (s, 3H);HRMS (ES) calcd for C₁₄H₁₃N₃O₆ 319.0804, found 319.0797.

[0587] EX-1B) A solution of1-Benzyl-3-methoxycarbonylmethyl-5-nitro-2,4(1H,3H) pyrimidinedione(EX-1A; 6.30 g, 19.74 mmol) in 100.0 mL methanol was degassed withhydrogen gas. The solution was then added 5% Pd/C (0.737 g) and allowedto stir under an atmosphere of hydrogen at room temperature for 24hours. The crude reaction was filtered through a pad of Celite 545 andconcentrated under reduced pressure. The oil was purified by MPLC (60%Ethyl acetate/hexanes) to give pure5-amino-1-Benzyl-3-methoxycarbonylmethyl-2,4(1H,3H)-pyrimidinedione(EX-1B) in 63% yield as a tan solid: ¹H NMR (300 MHz, DMSO) δ 7.41-7.28(m, 5H), 6.93 (s, 1H), 4.93 (s, 2H), 4.66 (s, 2H), 4.32 (s, 2H),3.69(s,3H); HRMS (ES) calcd for C₁₄H₁₆N₃O₄ 290.1141, found 290.1138.

[0588] EX-1C) A solution of5-amino-1-Benzyl-3-methoxycarbonylmethyl-2,4(1H,3H) pyrimidinedione(EX-1B; 3.12 g, 10.77 mmol) in 18.0 mL of tetrahydrofuran anddimethylformamide (1:1, 0.62M) was added N-methyl morpholine (3.60 mL,32.74 mmol) in one portion at room temperature. The resulting mixturewas cooled to 0° C. in an ice bath and was allowed to stir for 15minutes. A solution of benzylsulfonyl chloride (2.26 g, 11.86 mmol) in18.0 mL tetrahydrofuran was added drop wise over a 30 minute period.After the addition was complete the reaction was stirred for 3 hours at0° C. The reaction mixture was diluted with ethyl acetate (250.0 mL) andwashed with 1N HCl ((2×50 mL), saturated NaHCO3 (2×50 mL), and brine(2×50 mL). The organic solution was dried (MgSO₄), filtered andconcentrated. Trituration with ethyl acetate and hexanes gave pure1-Benzyl3-methoxycarbonylmethyl-5-[[(phenylmethyl)sulfonyl]amino]-2,4(1H,3H)pyrimidinedione(EX-1C) in 74% yield as a white solid: ¹H NMR (300 MHz, DMSO) δ 9.16 (s,1H), 8.02 (s, 1H), 7.43-7.37 (m, 10H), 5.01 (s, 2H), 4.65 (s, 2H), 4.45(s, 2H), 3.69 (s, 3H); HRMS (ES) calcd for C₂₁H₂₂N₃O₆S 444.1229, found444.1242.

[0589] EX-1D) A suspension of1-benzyl-3-methoxycarbonylmethyl-5-[[(phenylmethyl)sulfonyl]amino]-2,4(1H,3H)pyrimidinedione (EX-1C; 3.28 g, 7.40 mmol) in94.0 mL tetrahydrofuran and methanol (1:1, 0.078 M) was added 30.0 mL of0.1 M lithium hydroxide in water. The suspension quickly clears andbecomes homogeneous. The reaction was stirred for 1 hour, and thevolatiles were removed under reduced pressure. The remaining aqueoussolution was cooled in an ice bath and acidified to a pH of 1 with 1.0 NHCl which resulted in a white precipitate forming. The precipitate wascollected by filtration, washed with 1.0 N HCl and water, and driedunder vacuum to give pure 1-Benzyl3-methylene-carboxy-5-[[(phenylmethyl)sulfonyl]amino]-2,4(1H,3H)pyrimidinedione (EX -1D) in 99% yield: ¹H NMR(300 MHz, DMSO) δ 9.14 (br s, 1H), 7.98 (s, 1H), 7.44-7.35 (m, 10H),5.00 (s, 2H), 4.51 (s, 2H), 4.45 (s, 2H); HRMS (ES) calcd forC₂₀H₁₉N₃O₆S 429.0995, found 429.0981.

[0590] EX-1E) A solution of1-Benzyl-3-methylenecarboxy-5-[[(phenylmethyl)-sulfonyl]amino]-2,4(1H,3H)pyrimidinedione(EX-1D; 531.6 mg, 1.238 mmol) in 12.4 mL tetrahydrofuran anddimethylformamide (1:1, 0.1 M) was added N,N-diisopropylethylamine (1.10mL, 6.315 mmol), N-hydroxybenzotriazole (499.6 mg, 3.697 mmol), and1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (717.2 mg,3.741 mmol). The resulting mixture was allowed to stir for 30 minutes.The reaction mixture was then added amine (623.3 mg, 2.500 mmol) in oneportion. The resulting mixture was allowed to stir over night. Thereaction mixture was diluted with ethyl acetate (50 mL) and washed with5% citric acid (1×25 mL), saturated NaHCO₃ (1×25 mL), and brine (1×25mL). The organic solution was dried (MgSO₄), filtered and concentrated.The crude reaction was purified by MPLC (75% ethyl acetate/hexanes) togive the product EX-1E:

[0591]¹H NMR (300 MHz, DMSO) δ 9.13 (br s, 1H), 8.77 (t, J=5.3 Hz, 1H),7.98 (s, 1H), 7.91 (d, J=7.9 Hz, 1H), 7.45-7.35 (m, 13H), 5.01 (s, 2H),4.56 (s, 2H), 4.56 (s, 2H), 4.44 (s, 2H), 4.38 (d, J=5.4 Hz, 2H), 1.47(s, 9H); HRMS (ES) calcd for C₃₃H₃₇N₆O₇S 661.2444, found 661.2448.

[0592] A flask of protected pyrimidinedione (EX-1E) (238.5 mg, 0.3610mmol) was added 4.0 ml of 4 M HCl in dioxane. The resulting solution wasallowed to stir overnight (approximately 18 hours). The solution wasconcentrated and the crude product was triturated from ethyl ether. Theresulting white solid was collected by filtration, washed with ethylether and dried to give pure product: ¹H NMR (300 MHz, DMSO) δ 9.44 (s,2H), 9.29 (s, 2H), 9.14 (s, 1H), 9.01-8.99 (m, 1H), 7.99 (s, 1H), 7.81(d, J=7.9 Hz, 1H), 7.51-7.37 (m, 14H), 5.01 (s, 2H), 4.57 (s, 2H),4.45-4.41 (m, 2H), 3.58 (s, 2H); HRMS (ES) calcd for C₂₈H₂₉N₆O₅S561.1920, found 561.1917.

[0593] (EX-2A) A solution of1-Benzyl-3-methylenecarboxy-5-[[(phenyl-methyl)sulfonyl]amino]-2,4(1H,3H)pyrimidinedione(439.8 mg, 1.024 mmol) in 10.0 mL tetrahydrofuran and dimethylformamide(1:1, 0.1 M) was added N,N-diisopropylethylamine (1.80 mL, 10.30 mmol),N-hydroxybenzotriazole (169.3 mg, 1.253 mmol), and1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (238.2 mg,1.243 mmol). The resulting mixture was allowed to stir for 10 minutes.The reaction mixture was then added amine (648.3 mg, 1.231 mmol) in oneportion. The resulting mixture was allowed to stir over night. Thereaction mixture was diluted with ethyl acetate (100 mL) and washed with5% citric acid (1×50 mL), saturated NaHCO₃ (1×50 mL), and brine (1×50mL). The organic solution was dried (MgSO₄), filtered and concentrated.The crude reaction was purified by MPLC (75% ethyl acetate/hexanes) togive the product EX-2A: ¹H NMR (300 MHz, DMSO) δ 9.09 (s, 1H), 8.78 (d,J=7.1 Hz, 1H), 8.28 (d, J=3.0 Hz, 1H), 8.19 (d, J=3.0 Hz, 1H), 7.94 (s,1H), 7.43-7.31 (m, 10H), 6.68(s, 1H), 5.44-5.43 (m, 1H), 4.97 (s, 2H),4.56 (d, J=4.2 Hz, 2H), 4.41 (s, 2H), 3.80 (s, 3H), 3.08 (br d, J=5.4Hz, 3H), 2.91 (s, 1H), 2.75 (s, 1H), 2.59(s, 3H), 2.52 (s, 3H), 2.06 (s,3H), 1.92-1.80 (m, 1H), 1.61-1.51 (m, 3H), 1.37-1.33 (m 1H); HRMS (EI)calcd for C₃₉H₄₅N₈O₉S₃ 865.2472, found 865.2484.

[0594] A solution of EX-2A (281.3 mg, 0.3252 mmol) in 3.0 mLtrifluoroacetic acid (0.1 M) was added thioanisole (0.115 mL, 0.9796mmol) at room temperature with stirring. The resulting mixture wasallowed to stir 6 hours. The reaction mixture was concentrated underreduced pressure. The crude product was purified by trituration fromethyl ether. A light yellow powder was collected by filtration, washedwith ethyl ether to give pure product 2: ¹H NMR (300 MHz, DMSO) δ 9.07(s, 1H), 8.82 (d, J=7.0 Hz, 1H), 8.30 (d, J=3.0 Hz, 1H), 8.21 (d, J=3.0Hz, 1H), 7.95 (s, 1H), 7.55-7.20 (m, 10H), 5.49-5.48 (m, 1H), 4.97 (s,2H), 4.63-4.51 (m, 2H), 4.42 (s, 2H), 3.13 (br d, J=6.0 Hz, 2H), 2.49(s, 3H), 1.91 (br s, 1H), 1.67-1.58 (m, 4H); LRMS (EI), (MH+) 653.2.

[0595] Using the procedures exemplified in Examples 1 and 2 and theattached Scheme 1, the following compounds can be prepared.

[0596] Following Steps A and B exemplified in Example 1 and replacingbenzyl bromide with 3-(N-Boc-amino)benzyl bromide (Murakami, Y.;Hagishita, S.; Okada, T.; Kii, M.; Hashizume, H.; Yagami, T.; Fujimoto,M.; Bioorg. Med. Chem. 1999, 7, 1703-1714.), alkylated intermediate,methyl 3-[1-[3-(N-Boc-amino)benzyl]-5-amino-2,4-dioxopyrimidinyl]acetate(EX-3A) can be prepared.

[0597] To a solution of 1 eq. of ester EX-3A and 1 eq. of cyclobutanonein tetrahydrofuran is added 1 eq. of sodium cyanoborohydride, and themixture is stirred for several hours. The solvent is evaporated off toafford the crude product. The crude product is purified by silica gelchromatagraphy to afford purified methyl2-[3-[1-[3-(N-Boc-amino)benzyl]-5-(N-cyclobutyl)amino-2,4-dioxopyrimidinyl]]-acetate(EX-3B).

[0598] Following the remaining procedure exemplified in Example 1, theindicated compound of Example 3 can be obtained.

[0599] A solution of 1 eq. of the appropriate amide and 1 eq. of3-nitropnenylisocyanate in DMF is heated to 100° C. for several hours.The solvent is evaporated off to afford the crude product. The crudeproduct is purified by silica gel chromatagraphy to afford purifiedproduct 1-[3-Nitrophenyl]-5-nitro-2,4-dioxopyrimidine (EX-4A)

[0600] A solution of 1 eq. of uracil EX-4A in dimethylsulfoxide is addedto 1.1 eq. of potassium dicarbonate in one portion with stirring. Afterapproximately 10 minutes a solution containing 1.1 eq. of methylbromoacetate in dimethylsulfoxide is added dropwise over a 10 minuteperiod. The reaction mixture is heated to 40° C. and allowed to stir for18 hours. The reaction mixture is diluted with water. The aqueoussolution is extracted with ethyl acetate and the combined organicsolution is washed with water and brine. The organic solution is driedover MgSO₄, filtered, and concentrated to give a crude product. Thecrude product is purified by silica gel chromatagraphy to affordpurified methyl2-[3-[1-[3-nitrophenyl]-5-nitro-2,4-dioxopyrimidinyl]]acetate (EX-4B).

[0601] A suspension of methyl ester EX-4B in tetrahydrofuran andmethanol is added excess lithium hydroxide in water. The reaction isstirred for 1 hour, and the volatiles are removed under reducedpressure. The remaining aqueous solution is cooled in an ice bath andacidified to a pH of 1 with 1.0 N HCl which results in a whiteprecipitate forming. The precipitate is collected by filtration, washedwith 1.0 N HCl and water, and dried under vacuum to give pure acid,2-[3-[1-[3-nitrophenyl]-5-nitro-2,4-dioxopyrimidinyl]]acetic acid(EX-4C).

[0602] A solution of acid EX-4C in dimethylformamide (0.1 M) is added to5 eq N,N-diisopropylethylamine, 1 eq N-hydroxybenzotriazole mmol), and 1eq 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride. Theresulting mixture is allowed to stir for 30 minutes. To the reactionmixture is then added 1 eq. of 4-(N-Boc-amidino)benzylamine in oneportion. The resulting mixture is allowed to stir over night. Thereaction mixture is diluted with ethyl acetate and washed with 5% citricacid, saturated NaHCO₃, and brine. The organic solution is dried(MgSO₄), filtered and concentrated. Purification by MPLC pure,N-[4-(N-Boc-amidinobenzyl)]-2-[3-[1-[3-nitrophenyl]-5nitro-2,4-dioxopyrimidinyl]]acetamide(EX-4D).

[0603] A solution of bis-nitro compound EX-4D in methanol is treatedwith 5 molar percent of 10% Pd/C under an atmosphere of hydrogen(balloon pressure). The suspension is allowed to stir over night.Filtration through Celite 545 followed by removal of the solvent affordspure,N-[4-(N-Boc-amidinobenzyl)]-2-[3-[1-[3-aminophenyl]-5-amino-2,4-dioxopyrimidinyl]]acetamide(EX-4E).

[0604] A solution of bis-amine EX-4E and 1 eq. of cyclobutanone intetrahydrofuran is treated with 1 eq of sodium cyanoborohydride followedby a catalytic amount of hydrochloric acid. The reaction mixture isallowed to stir at room temperature for several hour. The reaction isquenched with the cautious addition of water. The aqueous solution isextracted with ethyl acetate. The organic solutions are washed withwater and brine. The organic solution is dried (MgSO₄), filtered andconcentrated. Purifaction by MPLC affords pure,N-[4-(N-Boc-amidinobenzyl)]-2-[3-[1-[3-aminophenyl]-5-(N-cyclobutyl-amino)-2,4-dioxopyrimidinyl]]acetamide(EX-4F).

[0605] A solution of N-Boc amidine EX-4F in methanol is treated with 3eq of 4 M HCl in dioxane. The solution is stirred for five hours.Removal of the solvents under vacuum followed by trituration with ethylether affords pure product.

[0606] A wide variety of methylene analogs of pyrimidinediones wherein amethylene is present as a replacement for the carbonyl of the acetamideat the N-2 position of the pyrimidinedione can be prepared using theprocedure detailed below

[0607] EX-5A) A solution of 1 eq. of phenyl isocyanate and 1 eq. of3-ethoxy-2-nitro-propenamide in DMF is heated to 100° C. for severalhours. The solvent is evaporated off to afford the crude product. Thecrude product is purified by silica gel chromatagraphy to affordpurified product EX-5A.

[0608] EX-5B) To a solution of 1 eq. of EX-5A in dimethylsulfoxide isadded to 1.1 eq. of potassium dicarbonate in one portion with stirring.After approximately 10 minutes, a solution containing 1.1 eq. of methylbromoacetate in dimethylsulfoxide is added dropwise over a 10 minuteperiod. The reaction mixture is heated to 40° C. and allowed to stir for18 hours. The reaction mixture is diluted with water. The aqueoussolution is extracted with ethyl acetate and the combined organicsolution is washed with water and brine. The organic solution is driedover MgSO₄, filtered, and concentrated to give a crude product. Thecrude product is purified by silica gel chromatagraphy to affordpurified product methyl2-[3-[5-nitro-2,4-dixoxo-1-phenylpyrimidyl]]acetate (EX-5B).

[0609] EX-5C) Diisobutylaluminum hydride (1.05 equiv.) is added over aperiod of 15 min to a cooled solution −78° C. of 1 eq. of EX-5B intetrahydrofuran . After stirring for 1 h at −78° C., the reaction isslowly quenched at −78° C. with cold methanol. The mixture is slowlypoured into ice-cold 1N HCl, and the aqueous mixture is extracted withethyl acetate. The combined organic layers are washed with brine, driedwith MgSO₄, filtered, and the solvents are removed under reducedpressure. The crude product is purified by column chromatagraphy toafford purified aldehyde product EX-5C.

[0610] EX-5D) A suspension of 1.0 eq. of the aldehyde,2-[3-[5-nitro-2,4-dixoxo-1-phenylpyrimidyl]]ethanal (EX-5C) and 1.0 eq.of the amine, 4-(N-Boc-amidino)benzylamine in dichloromethane, andcatalytic acetic acid is added 1.2 eq. of sodium triacetoxyborohydride.The suspension quickly clears and becomes homogeneous. The reaction isstirred for several hours. The solution is cooled in an ice bath and ismade alkaline with 1.0 N NaOH. The reaction mixture is diluted withdichloromethane and washed with brine. The organic solution is dried(MgSO₄), filtered and concentrated to give the crude product. The crudeproduct is purified by silica gel chromatagraphy to afford purifiedproduct2-[3-2-[2-[2-(4-(N-Boc-amidino)benzyl)amino]ethyl-5-nitro-2,4-dioxo-1-phenylpyrimidine(EX-5D):

[0611] EX-5E) A solution of 1 eq. of EX-5D in methanol is degassed withhydrogen gas. To the solution is added a catalytic amount of 5% Pd/C,and the reaction mixture is allowed to stir under an atmosphere ofhydrogen at room temperature for 24 hours. The crude reaction isfiltered through a pad of Celite 545 and concentrated under reducedpressure. The crude product is purified by silica gel chromatagraphy toafford purified product amine,2-[3-2-[2-[2-(4-(N-Boc-amidino)benzyl)amino]ethyl-5-amino-2,4-dioxo-1-phenylpyrimidine(EX-5E).

[0612] EX-5F) To a suspension of 1.0 eq. of EX-5E and 1.0 eq. of thephenylacetaldehyde in dichloromethane and catalytic acetic acid is added1.2 eq. of sodium triacetoxyborohydride. The suspension quickly clearsand becomes homogeneous. The reaction is stirred for several hours. Thesolution is cooled in an ice bath and basified with 1.0 N NaOH. Thereaction mixture is diluted with dichloromethane and washed with brine.The organic solution is dried (MgSO₄), filtered and concentrated to givethe crude product. The crude product is purified by silica gelchromatagraphy to afford purified2-[3-2-[2-[2-(4-(N-Boc-amidino)benzyl)amino]ethyl-5-(N-(2-phenylethyl)amino)-2,4-dioxo-1-phenylpyrimidine(EX-5F).

[0613] To a flask of 1 eq. of EX-5F is added 4 M HCl in dioxane. Theresulting solution is allowed to stir overnight. The solution isconcentrated and the crude product is triturated from ethyl ether toafford purified product as the dihydrochloride salt.

[0614] Sulfonyl analogs of pyrimidinediones wherein a sulfonyl ispresent as a replacement for the carbonyl of the acetamide at the N-2position of the pyrimidinedione can be prepared as detailed below in thespecific Example 6.

[0615] EX-6A) A solution of 1 eq. of EX-5A in dimethylsulfoxide is addedto 1.1 eq. of potassium dicarbonate in one portion with stirring. Afterapproximately 10 minutes, a solution containing 1.1 eq. of sodiumbromomethylsulfonate in dimethylsulfoxide is added dropwise over a 10minute period. The reaction mixture is heated to 40° C. and allowed tostir for 18 hours. The reaction mixture is diluted with water. Theaqueous solution is extracted with ethyl acetate. The combined organicsolutions are washed with water and brine. The organic solution is driedover MgSO₄, filtered, and concentrated to give a crude product. Thecrude product is purified by silica gel chromatagraphy to affordpurified product,3-[5-nitro-2,4-dixoxo-1-phenylpyrimidyl]methanesulfonic acid (EX-6A).

[0616] EX-6B) A solution of 1 eq. of EX-6A in methanol is degassed withhydrogen gas. To the solution is added a catalytic amount of 5% Pd/C,and the reaction mixture is allowed to stir under an atmosphere ofhydrogen at room temperature for 24 hours. The crude reaction isfiltered through a pad of Celite 545 and concentrated under reducedpressure. The crude product is purified by silica gel chromatagraphy toafford purified product,3-[5-amino-2,4-dixoxo-1-phenylpyrimidyl]methanesulfonic acid (EX -6B).

[0617] EX-6C) To a suspension of 1.0 eq. of EX-6B and 1.0 eq. of thephenylacetaldehyde in dichloromethane and catalytic acetic acid is added1.2 eq. of sodium triacetoxyborohydride. The reaction is stirred forseveral hours. The solution is cooled in an ice bath and basified with1.0 N NaOH. The reaction mixture is diluted with dichloromethane andwashed with brine. The organic solution is dried (MgSO₄), filtered andconcentrated to give the crude product. The crude product is purified bysilica gel chromatagraphy to afford purified product,3-[5-[N-(2-phenylethyl)amino]-2,4-dixoxo-1-phenylpyrimidyl]methanesulfonicacid (EX-6C).

[0618] EX-6D) A solution of 1 eq. of EX-6C in dichloromethane withseveral drops of dimethylformamide is cooled to 0° C. Thionyl chloride(1.1 equiv.) is added dropwise, and the solution is slowly warmed toroom temperature. After completion of the reaction, the volatilecomponents are removed under reduced pressure, and the sulfonyl chlorideproduct is immediately used. The sulfonyl chloride is dissolved intodichloromethane, and 1 eq. of the appropriate amine,4-(N-Boc-amidino)benzylamine, in DMF is added with 5 eq. ofN-methylmorpholine to the sulfonyl chloride solution. After completionof the reaction, polyaldehyde and/or polyamine resin (10 equiv.) areadded to remove any unreacted starting materials. The resins arefiltered, rinsed with DMF/DCM (1:1), and the solvents are removed underreduced pressure to give pureN-[4-(N-Boc-amidino)benzyl]-3-[5-[N-(2-phenylethyl)amino]-2,4-dixoxo-1-phenylpyrimidyl]methanesulfonamide(EX-6D).

[0619] A flask of 1 eq. of EX-6D is added to 4 M HCl in dioxane. Theresulting solution is allowed to stir overnight. The solution isconcentrated and the crude product was triturated from ethyl ether toafford purified product of Example 6.

[0620] Triazinedione (aza analogs) of uracils (i.e.,pyrimidinones)wherein a nitrogen is present as a replacement for the carbon at the5-position of the pyrimidinedione can be prepared as detailed below withthe specific Example 7.

[0621] EX-7A) A mixture of aniline (1; 50 mmol), concentrated HCl (10mL), and water (50 mL) is cooled to 5° C. Separately, a solution ofsodium nitrite (50 mmol) in water (7.2 mL) is cooled to 5° C. and addedto the aniline hydrochloride slurry with the addition tube beneath theliquid surface. The temperature is maintained at 5° C. during theaddition and for 1 hour thereafter. This solution of diazotized aniline(EX-7A) is used in the next step.

[0622] EX-7B) A mixture of cyanoacetylurethane (59 mmol), pyridine (656mL), ice (216 g) and water (40 mL) is held at 5° C. while the slurry ofEX-67A is added over 15 min with stirring. After an additional hour ofstirring at 5° C., the orange solid,N-ethoxycarbonyl-2-cyano-2-(N-phenylhydrazo)acetamide (EX-7B is isolatedby filtration.

[0623] EX-7C) A mixture of EX-7B (95 mmol), sodium acetate (110 mmol)and acetic acid (140 mL) is refluxed for 75 min. The resulting clearsolution is concentrated at reduced pressure, and the solid thatseparates is removed by filtration and washed with water. Compound,6-cyano-2-phenyl-3,5-dioxo-1,2,4-triazine (EX-7C), is recrystallizedfrom 95% ethanol.

[0624] EX-7D) A mixture of compound EX-7C (50 mmol), 6 N HCl (190 mL)and dioxane (500 mL) is refluxed for 12 h. On cooling the crystallizedproduct, 6-(2-phenyl-3,5-dioxo-1,2,4-triazinyl)carboxylic acid (EX-7D)is separated by filtration and recrystallized from methanol-water.

[0625] EX-7E) The acid EX-7D (8.4 mmol) is dissolved in dry tert-butylalcohol (127 mL) and DPPA (9.3 mmol), and triethyl amine (9.3 mmol) isadded. The solution is refluxed for 24 h thereafter. At this time thesolution is concentrated in vacuo. The residue is dissolved in methylenechloride (150 mL) and washed with 0.5 N citric acid (150 mL), 1 N NaHCO₃(150 mL) and water (150 mL). The methylene chloride solution is thendried (sodium sulfate). Filtration and concentration gives theBoc-protected compound EX-7E. This material can be purified bychromatagraphy if necessary.

[0626] EX-7F) A solution of compound EX-7E (50 mmol) in DMF (150 mL) istreated with potassium carbonate (55 mmol) in one portion with stirring.After approximately 10 min, a solution of methyl bromoacetate (50 mmol)in DMF (100 mL) is added dropwise. The reaction mixture is heated to 40°C. and allowed to stir for 18 h. Typical aqueous workup andchromatographic purification provides pure methyl2-(2-phenyl-3,5-dioxo-6-(N-Boc-amino)-1,2,4-triazinyl)acetate (EX-7F).

[0627] EX-7G) A solution of compound EX-7F (50 mmol) is dissolved inmethylene chloride (400 mL) and is treated with TFA (100 mL). Theresulting solution is stirred at room temperature for 4 h thereafter.Concentration and trituration with ether affords TFA salt of methyl2-(2-phenyl-3,5-dioxo-6-amino-1,2,4-triazinyl)acetate (EX-7G).

[0628] EX-7H) A solution of compound EX-7G in tetrahydrofuran andmethylene chloride (1:1, 0.3 M) is treated with 1 eq. ofphenylacetaldehyde and 0.9 eq. of triethyl amine. The solution will becooled to 0° C. and treated with 1 eq. of sodium triacetoxyborohydride.After stirring for 5 minutes, the ice bath is removed, and the reactionmixture is allowed to warm to room temperature and stir there for 2 h.The reaction is quenched by the addition of 1 N NaOH, and the mixture isstirred for 5 min. Typical aqueous workup is followed by chromatographicpurification to provide pure product, methyl2-(2-phenyl-3,5-dioxo-6-(N-(2-phenylethyl)amino)-1,2,4-triazinyl)acetate(EX-7H).

[0629] EX-7I) A solution of compound EX-7H (50 mmol) in THF (250 mL) istreated with LiOH (50 mmol). After the hydrolysis is complete, thevolatiles are removed under reduced pressure. The remaining aqueoussolution is cooled in an ice bath and acidified to pH 1 with 1.0 N HCl.The aqueous mixture is extracted with EtOAc. The EtOAc solution is dried(sodium sulfate), filtered and concentrated to afford pure2-(2-phenyl-3,5-dioxo-6-(N-(2-phenylethyl)amino)-1,2,4-triazinyl)aceticacid EX-7I).

[0630] EX-7J) A solution of compound EX-7I (50 mmol) in DMF (250 mL) istreated with N-hydroxybenzotriazole (60 mmol) and EDC hydrochloride (60mmol). The mixture is stirred at room temperature for 30 min and treatedwith 4-(N-Cbz-amidinobenxylamine (50 mmol). The resulting mixture isallowed to stir overnight. Typical aqueous workup is followed bychromatographic purification to afford pure product,N-(4-Cbz-amidinobenzyl)-2-(2-phenyl-3,5-dioxo-6-(N-(2-phenylethyl)amino)-1,2,4-triazinyl)acetamide(EX-7J).

[0631] A solution of compound EX-7J (50 mmol) in methanol (300 mL) and4M HCl-dioxane (100 mL) is degassed with hydrogen. 5% Pd(C) (0.5 g) isadded, and the solution is stirred under an atmosphere of hydrogen atroom temp for 24 h. The reaction mixture is filtered through a pad ofcelite 545 and concentrated under reduced pressure. Purification byreverse phase chromatagraphy affords pure product of Example 7.

[0632] Using these methods and ordinary skill in the art of syntheticnumerous novel compounds of the present invention have been or can beprepared.

[0633] Formula (I) compounds of this invention possessing hydroxyl,thiol, and amine functional groups can be converted to a wide varietyderivatives. Alternatively, derivatized Formula (I) compounds can beobtained by first derivatizing one or more intermediates in theprocesses of preparation before further transforming the derivatizedintermediate to compounds of Formula (I). A hydroxyl group in the formof an alcohol or phenol can be readily converted to esters ofcarboxylic, sulfonic, carbamic, phosphonic, and phosphoric acids.Acylation to form a carboxylic acid ester is readily effected using asuitable acylating reagent such as an aliphatic acid anhydride or acidchloride. The corresponding aryl and heteroaryl acid anhydrides and acidchlorides can also be used. Such reactions are generally carried outusing an amine catalyst such as pyridine in an inert solvent. Similarly,carbamic acid esters (urethanes) can be obtained by reacting a hydroxylgroup with isocyanates and carbamoyl chlorides. Sulfonate, phosphonate,and phosphate esters can be prepared using the corresponding acidchloride and similar reagents. Compounds of Formula (I) that have atleast one thiol group present can be converted to the correspondingthioesters derivatives analogous to those of alcohols and phenols usingthe same reagents and comparable reaction conditions. Compounds ofFormula (I) that have at least one primary or secondary amine grouppresent can be converted to the corresponding amide derivatives. Amidesof carboxylic acids can be prepared using the appropriate acid chlorideor anhydrides with reaction conditions analogous to those used withalcohols and phenols. Ureas of the corresponding primary or secondaryamine can be prepared using isocyanates directly and carbamoyl chloridesin the presence of an acid scavenger such as triethylamine or pyridine.Sulfonamides can be prepared from the corresponding sulfonyl chloride inthe presence of aqueous sodium hydroxide or a tertiary amine. Suitableprocedures and methods for preparing these derivatives can be found inHouse's Modern Synthetic Reactions, W. A. Benjamin, Inc., Shriner,Fuson, and Curtin in The Systematic Identification of Organic Compounds,5th Edition, John Wiley & Sons, and Fieser and Fieser in Reagents forOrganic Synthesis, Volume 1, John Wiley & Sons. Reagents of a widevariety that can be used to derivatize hydroxyl, thiol, and amines ofcompounds of Formula (I) are available from commercial sources or thereferences cited above, which are incorporated herein by reference.

[0634] Formula (I) compounds of this invention possessing hydroxyl,thiol, and amine functional groups can be alkylated to a wide variety ofderivatives. Alternatively, alkylated Formula (I) compounds can beobtained by first alkylating one or more intermediates in the processesof preparation before further transforming the alkylated intermediate tocompounds of Formula (I). A hydroxyl group of compounds of Formula (I)can be readily converted to ethers. Alkylation to form an ether isreadily effected using a suitable alkylating reagent such as an alkylbromide, alkyl iodide or alkyl sulfonate. The corresponding aralkyl,heteroaralkyl, alkoxyalkyl, aralkyloxyalkyl, and heteroaralkyloxyalkylbromides, iodides, and sulfonates can also be used. Such reactions aregenerally carried out using an alkoxide forming reagent such as sodiumhydride, potassium t-butoxide, sodium amide, lithium amide, and n-butyllithium using an inert polar solvent such as DMF, DMSO, THF, andsimilar, comparable solvents. amine catalyst such as pyridine in aninert solvent. Compounds of Formula (I) that have at least one thiolgroup present can be converted to the corresponding thioetherderivatives analogous to those of alcohols and phenols using the samereagents and comparable reaction conditions. Compounds of Formula (I)that have at least one primary, secondary or tertiary amine grouppresent can be converted to the corresponding secondary, tertiary orquaternary ammonium derivative. Quaternary ammonium derivatives can beprepared using the appropriate bromides, iodides, and sulfonatesanalogous to those used with alcohols and phenols. Conditions involvereaction of the amine by warming it with the alkylating reagent with astoichiometric amount of the amine (i.e., one equivalent with a tertiaryamine, two with a secondary, and three with a primary). With primary andsecondary amines, two and one equivalents, respectively, of an acidscavenger are used concurrently. Secondary or tertiary amines can beprepared from the corresponding primary or secondary amine. A primaryamine can be dialkylated by reductive amination using an aldehyde, suchas formaldehyde, and sodium cyanoborohydride in the presence of glacialacetic acid. A primary amine can be monoalkylated by firstmono-protecting the amine with a ready cleaved protecting group, such astrifluoroacetyl. An alkylating agent, such as dimethylsulfate, in thepresence of a non-nucleophilic base, such as Barton's base(2-tert-butyl-1,1,3,3-tetramethylguanidine), gives the monomethylatedprotected amine. Removal of the protecting group using aqueous potassiumhydroxide gives the desired monoalkylated amine. Additional suitableprocedures and methods for preparing these derivatives can be found inHouse's Modern Synthetic Reactions, W. A. Benjamin, Inc., Shriner,Fuson, and Curtin in The Systematic Identification of Organic Compounds,5th Edition, John Wiley & Sons, and Fieser and Fieser in Reagents forOrganic Synthesis published by John Wiley & Sons. Perfluoroalkylderivatives can be prepared as described by DesMarteau in J. Chem. Soc.Chem. Commun. 2241 (1998). Reagents of a wide variety that can be usedto derivatize hydroxyl, thiol, and amines of compounds of Formula (I)are available from commercial sources or the references cited above,which are incorporated herein by reference.

Assays for Biological Activity TF-VIIa Assay

[0635] In this assay 100 nM recombinant soluble tissue factor and 2 nMrecombinant human factor VIIa are added to a 96-well assay platecontaining 0.4 mM of the substrate,N-Methylsulfonyl-D-phe-gly-arg-p-nitroaniline and either inhibitor orbuffer (5 mM CaCl₂, 50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA). Thereaction, in a final volume of 100 ul is measured immediately at 405 nmto determine background absorbance. The plate is incubated at roomtemperature for 60 min, at which time the rate of hydrolysis of thesubstrate is measured by monitoring the reaction at 405 nm for therelease of p-nitroaniline. Percent inhibition of TF-VIIa activity iscalculated from OD_(405 nm) value from the experimental and controlsample.

Xa Assay

[0636] 0.3 nM human factor Xa and 0.15 mMN-α-Benzyloxycarbonyl-D-arginyl-L-glycyl-L-arginine-p-nitroaniline-dihydrochloride(S-2765) are added to a 96-well assay plate containing either inhibitoror buffer (50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA). The reaction,in a final volume of 100 ul is measured immediately at 405 nm todetermine background absorbance. The plate is incubated at roomtemperature for 60 min, at which time the rate of hydrolysis of thesubstrate is measured by monitoring the reaction at 405 nm for therelease of p-nitroaniline. Percent inhibition of Xa activity iscalculated from OD_(405 nm) value from the experimental and controlsample.

Thrombin Assay

[0637] 0.28 nM human thrombin and 0.06 mMH-D-Phenylalanyl-L-pipecolyl-L-arginine-p-nitroaniline dihydrochlorideare added to a 96-well assay plate containing either inhibitor or buffer(50 mM Tris-HCl, pH 8.0, 100 mM NaCl, 0.1% BSA). The reaction, in afinal volume of 100 ul is measured immediately at 405 nm to determinebackground absorbance. The plate is incubated at room temperature for 60min, at which time the rate of hydrolysis of the substrate is measuredby monitoring the reaction at 405 nm for the release of p-nitroaniline.Percent inhibition of thrombin activity is calculated from OD_(405 nm)value from the experimental and control sample.

Trypsin Assay

[0638] 5 ug/ml trypsin, type IX from porcine pancreas and 0.375 mMN-α-Benzoyl-L-arginine-p-nitroanilide (L-BAPNA) are added to a 96-wellassay plate containing either inhibitor or buffer (50 mM Tris-HCl, pH8.0, 100 mM NaCl, 0.1% BSA). The reactions, in a final volume of 100 ulare measured immediately at 405 nm to determine background absorbance.The plate is incubated at room temperature for 60 min, at which time therate of hydrolysis of the substrate is measured by monitoring thereaction at 405 nm for the release of p-nitroaniline. Percent inhibitionof trypsin activity is calculated from OD_(405 nm) value from theexperimental and control sample.

[0639] Recombinant soluble TF, consisting of amino acids 1-219 of themature protein sequence was expressed in E. coli and purified using aMono Q Sepharose FPLC. Recombinant human VIIa was purchased fromAmerican Diagnostica, Greenwich, Conn. and chromogenic substrateN-Methylsulfonyl-D-phe-gly-arg-p-nitroaniline was prepared by AmericanPeptide Company, Inc., Sunnyvale, Calif. Factor Xa was obtained fromEnzyme Research Laboratories, South Bend, Ind., thrombin fromCalbiochem, La Jolla, Calif., and trypsin and L-BAPNA from Sigma, St.Louis, Mo. The chromogenic substrates S-2765 and S-2238 were purchasedfrom Chromogenix, Sweden.

[0640] The biological activity of the compounds of Examples 1 through 7as determined by the bioassay procedures is summarized in the Table 1.TABLE 1 Inhibitory Activity of Uracils toward Factor Xa, TF-VIIA,Thrombin II, and Trypsin II. Example TF-VIIA Thrombin II Factor XaTrpysin II Number IC50 (uM) IC50 (uM) IC50 (uM) IC50 (uM) 1 >100 13.025.6 0.4 2 12.9 0.3 0.2 0.2

What we claim is:
 1. A compound having the Formula:

or a pharmaceutically acceptable salt thereof, wherein; B is formula(V):

 wherein D¹, D², J¹, J² and K¹ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one is a covalent bond, no more than one of D¹, D², J¹, J² andK¹ is O, no more than one of D¹, D², J¹, J² and K¹ is S, one of D¹, D²,J¹, J² and K¹ must be a covalent bond when two of D¹, D², J¹, J² and K¹are O and S, and no more than four of D¹, D², J¹, J² and K¹ are N; R⁹,R¹⁰, R¹¹, R¹², R¹³, R³², R³³, R³⁴, R³⁵, and R³⁶ are independentlyselected from the group consisting of hydrido, acetamido, haloacetamido,amidino, guanidino, alkylenedioxy, haloalkylthio, alkanoyloxy, alkoxy,alkoxyalkyl, haloalkoxylalkyl, hydroxy, amino, alkoxyamino, nitro, loweralkylamino, alkylthio, alkylthioalkyl, alkylsulfinyl, alkylsulfonyl,alkylsulfonylalkyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl,heteroaryl, heterocyclyl, alkylsulfonamido, alkylaminosulfonyl,amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkanoyl,haloalkanoyl, alkyl, alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy,hydroxyhaloalkyl, hydroxyalkyl, aminoalkyl, haloalkoxyalkyl,carboxyalkyl, carboalkoxy, carboxy, carboxamido, carboxamidoalkyl, andcyano; R¹⁶, R¹⁹, R³², R³³, R³⁴, R³⁵, and R³⁶ are independentlyoptionally Q^(b) with the proviso that no more than one of R¹⁶ and R¹⁹is Q^(b) at the same time and that Q^(b) is Q^(be); B is optionallyselected from the group consisting of hydrido, trialkylsilyl, C2-C8alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8haloalkyl, wherein each member of group B may be optionally substitutedat any carbon up to and including 6 atoms from the point of attachmentof B to A with one or more of the group consisting of R³², R³³, R³⁴,R³⁵, and R³⁶; B is optionally selected from the group consisting ofC3-C12 cycloalkyl and C4-C9 saturated heterocyclyl, wherein each ringcarbon is optionally substituted with R³³, a ring carbon other than thering carbon at the point of attachment of B to A is optionallysubstituted with oxo provided that no more than one ring carbon issubstituted by oxo at the same time, ring carbons and a nitrogenadjacent to the carbon atom at the point of attachment are optionallysubstituted with R⁹ or R¹³, a ring carbon or nitrogen atom adjacent tothe R⁹ position and two atoms from the point of attachment is optionallysubstituted with R¹⁰, a ring carbon or nitrogen adjacent to the R¹³position and two atoms from the point of attachment is optionallysubstituted with R¹², a ring carbon or nitrogen three atoms from thepoint of attachment and adjacent to the R¹⁰ position is optionallysubstituted with R¹¹, a ring carbon or nitrogen three atoms from thepoint of attachment and adjacent to the R¹² position is optionallysubstituted with R³³, and a ring carbon or nitrogen four atoms from thepoint of attachment and adjacent to the R¹¹ and R³³ positions isoptionally substituted with R³⁴; A is selected from the group consistingof single covalent bond, (W⁷)_(rr)—(CH(R¹⁵))_(pa) and(CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected from 0through 1, pa is an integer selected from 0 through 6, and W⁷ isselected from the group consisting of O, S, C(O), (R⁷)NC(O), (R⁷)NC(S),and N(R⁷) with the proviso that no more than one of the group consistingof rr and pa is 0 at the same time; R⁷ is selected from the groupconsisting of hydrido, hydroxy, and alkyl; R¹⁵ is selected from thegroup consisting of hydrido, hydroxy, halo, alkyl, and haloalkyl; Ψ isselected from the group consisting of NH and NOH; M is selected from thegroup consisting of N and R¹—C; R¹ is selected from the group consistingof hydrido, alkyl, alkenyl, cyano, halo, haloalkyl, haloalkoxy,haloalkylthio, amino, aminoalkyl, alkylamino, amidino, hydroxy,hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, and alkylthio;R² is Z⁰—Q; Z⁰ is selected from the group consisting of covalent singlebond, (CR⁴¹R⁴²)_(q) wherein q is an integer selected from 1 through 3,(CH(R⁴¹))_(g)—W⁰—(CH(R⁴²))_(p) wherein g and p are integersindependently selected from 0 through 3 and W⁰ is selected from thegroup consisting of O, S, C(O), S(O), N(R⁴¹), and ON(R⁴¹), and(CH(R⁴¹))_(e)—W²²—(CH(R⁴²)_(h) wherein e and h are integersindependently selected from 0 through 1 and W²² is selected from thegroup consisting of CR⁴¹═CR⁴², 1,2-cyclopropyl, 1,2-cyclobutyl,1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl,2,3-morpholinyl, 2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl, 3,5morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl,2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl,2,4-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 1,2-pyrrolidinyl,1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl,3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,2,5-tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, with the proviso thatZ⁰ is directly bonded to the pyrazinone ring; R⁴¹ and R⁴² areindependently selected from the group consisting of amidino,hydroxyamino, hydrido, hydroxy, amino, and alkyl; Q is selected from thegroup consisting of hydrido, with the proviso that Z⁰ is other than acovalent single bond, and the formula (II):

 wherein D¹, D², J¹, J² and K¹ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one is a covalent bond, no more than one of D¹, D², J¹, J² andK¹ is O, no more than one of D¹, D², J¹, J² and K¹ is S, one of D¹, D²,J¹, J² and K¹ must be a covalent bond when two of D¹, D², J¹, J² and K¹are O and S, and no more than four of D¹, D², J¹, J² and K¹ are N, withthe proviso that R⁹, R¹⁰, R¹¹, R¹², and R¹³ are each independentlyselected to maintain the tetravalent nature of carbon, trivalent natureof nitrogen, the divalent nature of sulfur, and the divalent nature ofoxygen; K is (CR^(4a)R^(4b))_(n) wherein n is an integer selected from 1through 2; R^(4a) and R^(4b) are independently selected from the groupconsisting of halo, hydrido, hydroxyalkyl, alkyl, alkoxyalkyl,alkylthioalkyl, and haloalkyl; E⁰ is E¹, when K is (CR^(4a)R^(4b))_(n)wherein E¹ is selected from the group consisting of a covalent singlebond, C(O), C(S), C(O)N(R⁷), (R⁷)NC(O), S(O)₂, (R⁷)NS(O)₂, andS(O)₂N(R⁷); Y⁰ is formula (IV):

 wherein D⁵, D⁶, J⁵and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one is a covalent bond, K² is C, no more than one of D⁵, D⁶,J⁵and J⁶ is O, no more than one of D⁵, D⁶, J⁵and J⁶ is S, one of D⁵, D⁶,J⁵and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵and J⁶ are O andS, and no more than four of D⁵, D⁶, J⁵and J⁶ are N; R¹⁶, R¹⁷, R¹⁸, andR¹⁹ are independently selected from the group consisting of hydrido,amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy, amino,nitro, alkoxyamino, lower alkylamino, alkylthio, alkylsulfinyl,alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, alkenyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, alkylamino, haloalkoxyalkyl, carboalkoxy, andcyano; Q^(b) is selected from the group consisting of NR²⁰R²¹,aminoalkylenyl, Q^(be) wherein Q^(be) is hydrido,N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the provisos that nomore than one of R²⁰ and R²¹ is hydroxy, amino, alkylamino, ordialkylamino at the same time and that no more than one of R²³ and R²⁴is hydroxy, amino, alkylamino, or dialkylamino at the same time; R²⁰,R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from the groupconsisting of hydrido, alkyl, hydroxy, aminoalkylenyl, amino,dialkylamino, alkylamino, and hydroxyalkyl; Q^(s) is selected from thegroup consisting of a single covalent bond, (CR³⁷R³⁸)_(b) wherein b isan integer selected from 1 through 4, and (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d)wherein c and d are integers independently selected from 1 through 3 andW¹ is selected from the group consisting of C(O)N(R¹⁴), (R¹⁴)NC(O),S(O), S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, and N(R¹⁴), with the provisosthat R¹⁴ is selected from other than halo when directly bonded to N andthat (CR³⁷R³⁸)_(b), and (CH(R¹⁴))_(c) are bonded to E⁰; R¹⁴ is selectedfrom the group consisting of hydrido, halo, alkyl, and haloalkyl; R³⁷and R³⁸ are independently selected from the group consisting of hydrido,alkyl, and haloalkyl; R³⁸ is optionally selected from the groupconsisting of aroyl and heteroaroyl; Y⁰ is optionally Q^(b)—Q^(ss)wherein Q^(ss) is (CH(R¹⁴))_(e)—W²—(CH(R¹⁵))_(h), wherein e and h areintegers independently selected from 1 through 2 and W² isCR^(4a)═CR^(4b) with the proviso that (CH(R¹⁴))_(e) is bonded to E⁰; Y⁰is optionally selected from the group consisting of Q^(b)—Q^(ssss) andQ^(b)—Q^(ssssr) wherein Q^(ssss) is (CH(R³⁸))_(r)—W⁵ and Q^(ssssr) is(CH(R³⁸))_(r)—W⁶, r is an integer selected from 1 through 2, and W⁵ andW⁶ are independently selected from the group consisting of 1,4-indenyl,1,5-indenyl, 1,6-indenyl, 1,7-indenyl, 2,7-indenyl, 2,6-indenyl,2,5-indenyl, 2,4-indenyl, 3,4-indenyl, 3,5-indenyl, 3,6-indenyl,3,7-indenyl, 2,4benzofuranyl, 2,5-benzofuranyl, 2,6-benzofuranyl,2,7-benzofuranyl, 3,4-benzofuranyl, 3,5-benzofuranyl, 3,6-benzofuranyl,3,7-benzofuranyl, 2,4benzothiophenyl, 2,5-benzothiophenyl,2,6-benzothiophenyl, 2,7-benzothiophenyl, 3,4-benzothiophenyl,3,5-benzothiophenyl, 3,6-benzothiophenyl, 3,7-benzothiophenyl,2,7-imidazo(1,2-a)pyridinyl, 3,4-imidazo(1,2-a)pyridinyl,3,5imidazo(1,2-a)pyridinyl, 3,6-imidazo(1,2-a)pyridinyl,3,7-imidazo(1,2-a)pyridinyl, 2,4-indolyl, 2,5-indolyl, 2,6-indolyl,2,7-indolyl, 3,4-indolyl, 3,5-indolyl, 3,6-indolyl, 3,7-indolyl,1,4-isoindolyl, 1,5-isoindolyl, 1,6-isoindolyl, 2,4-isoindolyl,2,5-isoindolyl, 2,6-isoindolyl, 2,7-isoindolyl, 1,3-isoindolyl,3,4-indazolyl, 3,5-indazolyl, 3,6-indazolyl, 3,7-indazolyl,2,4benzoxazolyl, 2,5-benzoxazolyl, 2,6-benzoxazolyl, 2,7-benzoxazolyl,3,4-benzisoxazolyl, 3,5-benzisoxazolyl, 3,6-benzisoxazolyl,3,7-benzisoxazolyl, 1,4-naphthyl, 1,5-naphthyl, 1,6-naphthyl,1,7-naphthyl, 1,8-naphthyl, 2,4-naphthyl, 2,5-naphthyl, 2,6-naphthyl,2,7-naphthyl, 2,8-naphthyl, 2,4-quinolinyl, 2,5-quinolinyl,2,6-quinolinyl, 2,7-quinolinyl, 2,8-quinolinyl, 3,4quinolinyl,3,5-quinolinyl, 3,6-quinolinyl, 3,7-quinolinyl, 3,8-quinolinyl,4,5-quinolinyl, 4,6-quinolinyl, 4,7-quinolinyl, 4,8-quinolinyl,1,4-isoquinolinyl, 1,5-isoquinolinyl, 1,6-isoquinolinyl,1,7-isoquinolinyl, 1,8-isoquinolinyl, 3,4-isoquinolinyl,3,5-isoquinolinyl, 3,6-isoquinolinyl, 3,7-isoquinolinyl,3,8-isoquinolinyl, 4,5-isoquinolinyl, 4,6-isoquinolinyl,4,7-isoquinolinyl, 4,8-isoquinolinyl, 3,4-cinnolinyl, 3,5cinnolinyl,3,6-cinnolinyl, 3,7-cinnolinyl, 3,8-cinnolinyl, 4,5-cinnolinyl,4,6-cinnolinyl, 4,7-cinnolinyl, and 4,8-cinnolinyl, and each carbon andhyrido containing nitrogen member of the ring of the W⁵ and of the ringof the W⁶, other than the points of attachment of W⁵ and W⁶, isoptionally substituted with one or more of the group consisting of R⁹,R¹⁰, R¹¹, and R¹², with the provisos that Q^(b) is bonded to lowestnumber substituent position of each W⁵, Q^(b) is bonded to highestnumber substituent position of each W⁶, and (CH(R³⁸))_(r) is bonded toE⁰.
 2. The compound as recited in claim 1 having the Formula:

or a pharmaceutically acceptable salt thereof, wherein; B is selectedfrom the group consisting of aryl and heteroaryl wherein a carbonadjacent to the carbon at the point of attachment is optionallysubstituted by R³², the other carbon adjacent to the carbon at the pointof attachment is optionally substituted by R³⁶, a carbon adjacent to R³²and two atoms from the carbon at the point of attachment is optionallysubstituted by R³³, a carbon adjacent to R³⁶ and two atoms from thecarbon at the point of attachment is optionally substituted by R³⁵, andany carbon adjacent to both R³³ and R³⁵ is substituted by R³⁴; R³², R³³,R³⁴, R³⁵, and R³⁶ are independently selected from the group consistingof hydrido, acetamido, haloacetamido, amidino, guanidino, alkylenedioxy,haloalkylthio, alkanoyloxy, alkoxy, hydroxy, amino, alkoxyamino,haloalkanoyl, nitro, lower alkylamino, alkylthio, aryl, aralkyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido,amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl,alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl,alkylamino, carboalkoxy, carboxy, carboxamido, cyano, and Q^(b); B isoptionally selected from the group consisting of hydrido, trialkylsilyl,C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8haloalkyl, wherein each member of group B is optionally substituted atany carbon up to and including 6 atoms from the point of attachment of Bto A with one or more of the group consisting of R³², R³³, R³⁴, R³⁵, andR³⁶; B is optionally selected from the group consisting of C3-C12cycloalkyl and C4-C9 saturated heterocyclyl, wherein each ring carbon isoptionally substituted with R³³, a ring carbon other than the ringcarbon at the point of attachment of B to A is optionally substitutedwith oxo provided that no more than one ring carbon is substituted byoxo at the same time, ring carbons and a nitrogen adjacent to the carbonatom at the point of attachment are optionally substituted with R⁹ orR¹³, a ring carbon or nitrogen atom adjacent to the R⁹ position and twoatoms from the point of attachment is optionally substituted with R¹⁰, aring carbon or nitrogen adjacent to the R¹³ position and two atoms fromthe point of attachment is optionally substituted with R¹², a ringcarbon or nitrogen three atoms from the point of attachment and adjacentto the R¹⁰ position is optionally substituted with R¹¹, a ring carbon ornitrogen three atoms from the point of attachment and adjacent to theR¹² position is optionally substituted with R³³, and a ring carbon ornitrogen four atoms from the point of attachment and adjacent to the R¹¹and R³³ positions is optionally substituted with R³⁴; R⁹, R¹⁰, R¹¹, R¹²,and R¹³ are independently selected from the group consisting of hydrido,acetamido, haloacetamido, alkoxyamino, alkanoyl, haloalkanoyl, amidino,guanidino, alkylenedioxy, haloalkylthio, alkoxy, hydroxy, amino, loweralkylamino, alkylthio, alkylsulfinyl, alkylsulfamido, alkylsulfonyl,amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl,halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, carboalkoxy,carboxy, carboxyalkyl, carboxamido, and cyano; R⁹, R¹⁰, R¹¹, R¹², andR¹³ are optionally selected from the group consisting of heteroaryl andheterocyclyl with the proviso that R⁹, R¹⁰, R¹¹, R¹², and R¹³ aresubstitutents for other than B; A is selected from the group consistingof single covalent bond and (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is aninteger selected from 0 through 1, pa is an integer selected from 0through 3, and W⁷ is selected from the group consisting of O, S, C(O),(R⁷)NC(O), (R⁷)NC(S), and N(R⁷); R⁷ is selected from the groupconsisting of hydrido, hydroxy and alkyl; R¹⁵ is selected from the groupconsisting of hydrido, hydroxy, halo, alkyl, and haloalkyl; M isselected from the group consisting of N and R¹—C; R¹ is selected fromthe group consisting of hydrido, alkyl, cyano, halo, haloalkyl,haloalkoxy, amino, aminoalkyl, alkylamino, amidino, hydroxy,hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, and alkylthio;R² is Z⁰—Q; Z⁰ is selected from the group consisting of covalent singlebond and (CR⁴¹R⁴²)_(q) wherein q is an integer selected from 1 through2, (CH(R⁴¹))_(g)—W⁰—(CH(R⁴²))_(p) wherein g and p are integersindependently selected from 0 through 3 and W⁰ is selected from thegroup consisting of O, S, and N(R⁴¹), and(CH(R⁴¹))_(e)—W²²—(CH(R⁴²))_(h) wherein e and h are integersindependently selected from 0 through 1 and W²² is selected from thegroup consisting of CR⁴¹ ═CR⁴², 1,2-cyclopropyl, 1,2-cyclobutyl,1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl,2,3-morpholinyl, 2,4 morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl,3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl,2,6piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl,2,4-piperidinyl, 2,6piperidinyl, 3,4-piperidinyl, 1,2-pyrrolidinyl,1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5-pyrrolidinyl,3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,2,5Stetrahydrofuranyl, and 3,4-tetrahydrofuranyl, with the proviso thatZ⁰ is directly bonded to the pyrazinone ring; R⁴¹ and R⁴² areindependently selected from the group consisting of hydrido, hydroxy,and amino; Q is selected from the group consisting of hydrido, with theproviso that Z⁰ is other than a covalent single bond, aryl, andheteroaryl, wherein a carbon adjacent to the carbon at the point ofattachment is optionally substituted by R⁹, the other carbon adjacent tothe carbon at the point of attachment is optionally substituted by R¹³,a carbon adjacent to R⁹ and two atoms from the carbon at the point ofattachment is optionally substituted by R¹⁰, a carbon adjacent to R¹³and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹², and any carbon adjacent to both R¹⁰ and R¹² isoptionally substituted by R¹¹; K is CHR^(4a) wherein R^(4a) is selectedfrom the group consisting of hydrido, hydroxyalkyl, alkyl, alkoxyalkyl,alkylthioalkyl, and haloalkyl; E⁰ is selected from the group consistingof a covalent single bond, C(O)N(H), (H)NC(O), (R⁷)NS(O)₂, andS(O)₂N(R⁷); Y⁰ is formula (IV):

 wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one can be a covalent bond, K² is C, no more than one of D⁵,D⁶, J⁵, and J⁶ can be O, no more than one of D⁵, D⁶, J⁵, and J⁶ can beS, one of D⁵, D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶,J⁵, and J⁶ are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ canbe N, with the provisos that R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are eachindependently selected to maintain the tetravalent nature of carbon,trivalent nature of nitrogen, the divalent nature of sulfur, and thedivalent nature of oxygen; R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independentlyselected from the group consisting of hydrido, amidino, guanidino,carboxy, haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, loweralkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl,haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,aminoalkyl, and cyano; R¹⁶ and R¹⁹ are optionally Q^(b) with the provisothat no more than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and thatQ^(b) is Q^(be); Q^(b) is selected from the group consisting of NR²⁰R²¹,Q^(be) wherein Q^(be) is hydrido, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), andC(NR²⁵)NR²³R²⁴, with the provisos that no more than one of R²⁰ and R²¹is hydroxy, amino, alkylamino, or dialkylamino at the same time and thatno more than one of R²³ and R²⁴ is hydroxy, amino, alkylamino, ordialkylamino at the same time; R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ areindependently selected from the group consisting of hydrido, alkyl,hydroxy, amino, alkylamino and dialkylamino; Q^(s) is selected from thegroup consisting of a single covalent bond, (CR³⁷R³⁸)_(b) wherein b isan integer selected from 1 through 4, and (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d)wherein c and d are integers independently selected from 1 through 3 andW¹ is selected from the group consisting of C(O)N(R¹⁴), (R¹⁴)NC(O),S(O), S(O)₂, S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, and N(R¹⁴), with the provisosthat R¹⁴ is selected from other than halo when directly bonded to N andthat (CR³⁷R³⁸)_(b), and (CH(R¹⁴))_(c) are bonded to E⁰; R¹⁴ is selectedfrom the group consisting of hydrido, halo, alkyl, and haloalkyl; R³⁷and R³⁸ are independently selected from the group consisting of hydrido,alkyl, and haloalkyl; R³⁸ is optionally selected from the groupconsisting of aroyl and heteroaroyl; Y⁰ is optionally Q^(b)—Q^(ss)wherein Q^(ss) is (CH(R¹⁴))_(e)—W²—(CH(R¹⁵))_(h), wherein e and h areintegers independently selected from 1 through 2 and W² is CR^(4a)═CHwith the proviso that (CH(R¹⁴))_(e) is bonded to E⁰.
 3. The compound asrecited in claim 2 or a pharmaceutically acceptable salt thereof,wherein; B is selected from the group consisting of hydrido,trialkylsilyl, C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8alkynyl, and C2-C8 haloalkyl, wherein each member of group B isoptionally substituted at any carbon up to and including 6 atoms fromthe point of attachment of B to A with one or more of the groupconsisting of R³², R³³, R³⁴, R³⁵, and R³⁶; R³², R³³, R³⁴, R³⁵, and R³⁶are independently selected from the group consisting of hydrido,acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino,alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkylamidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, andQ^(b); A is (CH(R¹⁵))_(pa)—W⁷ wherein pa is an integer selected from 1through 3 and W⁷ is selected from the group consisting of O, S, andN(R⁷) wherein R⁷ is selected from the group consisting of hydrido andalkyl; R¹⁵ is selected from the group consisting of hydrido, hydroxy,halo, alkyl, and haloalkyl with the proviso that R¹⁵ is other thanhydroxy and halo when R¹⁵ is on the carbon bonded directly to W⁷; M isselected from the group consisting of N and R¹—C; R¹ is selected fromthe group consisting of hydrido, alkyl, cyano, halo, haloalkyl,haloalkoxy, amino, aminoalkyl, alkylamino, amidino, hydroxy,hydroxyamino, alkoxy, hydroxyalkyl, alkoxyamino, thiol, and alkylthio;R² is Z⁰—Q; Z⁰ is selected from the group consisting of covalent singlebond and (CR⁴¹R⁴²)_(q) wherein q is an integer selected from 1 through2; R⁴¹ and R⁴² are independently selected from the group consisting ofhydrido, hydroxy, and amino; Q is selected from the group consisting ofaryl and heteroaryl, wherein a carbon adjacent to the carbon at thepoint of attachment is optionally substituted by R⁹, the other carbonadjacent to the carbon at the point of attachment is optionallysubstituted by R¹³, a carbon adjacent to R⁹ and two atoms from thecarbon at the point of attachment is optionally substituted by R¹⁰, acarbon adjacent to R¹³ and two atoms from the carbon at the point ofattachment is optionally substituted by R¹², and any carbon adjacent toboth R¹⁰ and R¹² is optionally substituted by R¹¹; R⁹, R¹⁰, R¹¹, R¹²,and R¹³ are independently selected from the group consisting of hydrido,acetamido, haloacetamido, alkoxyamino, alkanoyl, haloalkanoyl, amidino,guanidino, alkylenedioxy, haloalkylthio, alkoxy, hydroxy, amino, loweralkylamino, alkylthio, alkylsulfinyl, alkylsulfamido, alkylsulfonyl,amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl,halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, carboalkoxy,carboxy, carboxyalkyl, carboxamido, and cyano; K is CHR^(4a) whereinR^(4a) is selected from the group consisting of hydrido, hydroxyalkyl,alkyl, alkoxyalkyl, alkylthioalkyl, and haloalkyl; E⁰ is selected fromthe group consisting of a covalent single bond, C(O)N(H), (H)NC(O),(R⁷)NS(O)₂, and S(O)₂N(R⁷); Y⁰ is formula (IV):

 wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one is a covalent bond, K² is C, no more than one of D⁵, D⁶,J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵,D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ are N; R¹⁶,R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group consistingof hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy,amino, alkoxyamino, lower alkylamino, alkylthio, alkylsulfinyl,alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, alkylamino, and cyano; R¹⁶ and R¹⁹ areoptionally Q^(b) with the proviso that no more than one of R¹⁶ and R¹⁹is Q^(b) at the same time and that Q^(b) is Q^(be); Q^(b) is selectedfrom the group consisting of NR²⁰R²¹, Q^(be) wherein Q^(be) is hydrido,N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the provisos that nomore than one of R²⁰ and R²¹ is hydroxy, amino, alkylamino, ordialkylamino at the same time and that no more than one of R²³ and R²⁴is hydroxy, amino, alkylamino, or dialkylamino at the same time; R²⁰,R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from the groupconsisting of hydrido, alkyl, hydroxy, amino, alkylamino anddialkylamino; Q^(s) is selected from the group consisting of a singlecovalent bond, (CR³⁷R³⁸)_(b) wherein b is an integer selected from 1through 3, and (CH(R¹⁴))_(c)—W¹—(CH(R¹⁵))_(d) wherein c and d areintegers independently selected from 1 through 2 and W¹ is selected fromthe group consisting of C(O)N(R¹⁴), (R¹⁴)NC(O), S(O), S(O)₂,S(O)₂N(R¹⁴), N(R¹⁴)S(O)₂, and N(R¹⁴), with the provisos that R¹⁴ isselected from other than halo when directly bonded to N and that(CR³⁷R³⁸)_(b), and (CH(R¹⁴))_(c) are bonded to E⁰; R¹⁴ is selected fromthe group consisting of hydrido, halo, alkyl, and haloalkyl; R³⁷ and R³⁸are independently selected from the group consisting of hydrido, alkyl,and haloalkyl; R³⁸ is optionally selected from the group consisting ofaroyl and heteroaroyl; Y⁰ is optionally Q^(b)—Q^(ss) wherein Q^(ss) is(CH(R¹⁴))_(e)—W²—(CH(R¹⁵))_(h), wherein e and h are integersindependently selected from 1 through 2 and W² is CR^(4a)═CH with theproviso that (CH(R¹⁴))_(e) is bonded to E⁰.
 4. The compound as recitedin claim 3 having the Formula:

or a pharmaceutically acceptable salt thereof, wherein; B is selectedfrom the group consisting of hydrido, trialkylsilyl, C2-C4 alkyl, C3-C5alkylenyl, C3-C4 alkenyl, C3-C4 alkynyl, and C2-C4 haloalkyl, whereineach member of group B is optionally substituted at any carbon up to andincluding 3 atoms from the point of attachment of B to A with one ormore of the group consisting of R³², R³³, and R³⁴; R³², R³³, R³⁴ areindependently selected from the group consisting of hydrido, acetamido,haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino,lower alkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl,dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,carboalkoxy, carboxy, carboxamido, and cyano; A is (CH(R¹⁵))_(pa)—N(R⁷)wherein pa is an integer selected from 1 through 2 and R⁷ is selectedfrom the group consisting of hydrido and alkyl; R¹⁵ is selected from thegroup consisting of hydrido, halo, alkyl, and haloalkyl; M is selectedfrom the group consisting of N and R¹—C; R¹ is selected from the groupconsisting of hydrido, hydroxy, hydroxyamino, amidino, amino, cyano,hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio,alkoxyamino, haloalkyl, haloalkoxy, and halo; R² is Z⁰—Q; Z⁰ is selectedfrom the group consisting of covalent single bond and CH₂; Q is selectedfrom the group consisting of aryl and heteroaryl, wherein a carbonadjacent to the carbon at the point of attachment is optionallysubstituted by R⁹, the other carbon adjacent to the carbon at the pointof attachment is optionally substituted by R¹³, a carbon adjacent to R⁹and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹⁰, a carbon adjacent to R¹³ and two atoms from thecarbon at the point of attachment is optionally substituted by R¹², andany carbon adjacent to both R¹⁰ and R¹² is optionally substituted byR¹¹; R⁹, R¹¹, and R¹³ are independently selected from the groupconsisting of hydrido, hydroxy, amino, amidino, guanidino, loweralkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl, alkylsulfonyl,amidosulfonyl, monoalkyl amidosulfonyl, alkyl, alkoxy, halo, haloalkyl,haloalkoxy, hydroxyalkyl, carboxy, carboxamido, and cyano; R¹⁰ and R¹²are independently selected from the group consisting of hydrido,acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy, hydroxy,amino, alkoxyamino, lower alkylamino, alkylsulfonamido, amidosulfonyl,monoalkyl amidosulfonyl, dialkyl amidosulfonyl, hydroxyalkyl,aminoalkyl, carboalkoxy, carboxy, carboxyalkyl, amidocarbonyl, halo,haloalkyl, and cyano; Y⁰ is formula (IV):

 wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one is a covalent bond, K² is C, no more than one of D⁵, D⁶,J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵,D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ are N; R¹⁶,R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group consistingof hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy,amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl,alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy,hydroxyalkyl, aminoalkyl, and cyano; R¹⁶ and R¹⁹ are optionally Q^(b)with the proviso that no more than one of R¹⁶ and R¹⁹ is Q^(b) at thesame time and that Q^(b) is Q^(be); Q^(b) is selected from the groupconsisting of NR²⁰R²¹, Q^(be) wherein Q^(be) is hydrido, C(NR²⁵)NR²³R²⁴,and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the provisos that no more than one ofR²⁰ and R²¹ is hydroxy at the same time and that no more than one of R²³and R²⁴ is hydroxy at the same time; R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶are independently selected from the group consisting of hydrido, alkyl,and hydroxy; Q^(s) is selected from the group consisting of a singlecovalent bond, CH₂, and CH₂CH₂.
 5. The compound as recited in claim 4having the Formula or a pharmaceutically acceptable salt thereof,wherein; B is selected from the group consisting of ethyl, 2-propenyl,2-propynyl, propyl, isopropyl, trimethylene, tetramethylene, butyl,2-butenyl, 3-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl,2-methylpropenyl, 2,2,2-trifluoroethyl, 3,3,3-trifluoropropyl, and2,2-difluoropropyl, wherein each member of group B is optionallysubstituted at any carbon up to and including 3 atoms from the point ofattachment of B to A with one or more of the group consisting of R³²,R³³, and R³⁴; R³², R³³, and R³⁴ are independently selected from thegroup consisting of hydrido, amidino, guanidino, carboxy, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,acetamido, trifluoroacetamido, N-methylamino, dimethylamino,N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, and cyano; A is selected from the groupconsisting of single covalent bond, NH, and N(CH₃); M is selected fromthe group consisting of N and R¹—C; R¹ is selected from the groupconsisting of hydrido, hydroxy, amino, amidino, hydroxyamino,aminomethyl, 1-aminoethyl, methylamino, dimethylamino, cyano, methyl,ethyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio,ethylthio, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro,and bromo; R² is Z⁰—Q; Z⁰ is selected from the group consisting of acovalent single bond and CH₂; Q is selected from the group consisting ofphenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl,3-isoxazolyl, 5isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl,2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl,4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a carbon adjacent to thecarbon at the point of attachment is optionally substituted by R⁹, theother carbon adjacent to the carbon at the point of attachment isoptionally substituted by R¹³, a carbon adjacent to R⁹ and two atomsfrom the carbon at the point of attachment is optionally substituted byR¹⁰, a carbon adjacent to R¹³ and two atoms from the carbon at the pointof attachment is optionally substituted by R¹², and any carbon adjacentto both R¹⁰ and R¹² is optionally substituted by R¹¹; R⁹, R¹¹, and R¹³are independently selected from the group consisting of hydrido,amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, N-methylamino,N,N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, and cyano; R¹⁰ and R¹² are independentlyselected from the group consisting of hydrido, amidino, guanidino,carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, fluoro,chloro, bromo, and cyano; Y⁰ is selected from the group consisting of:1-Q^(b)-4-Q^(s)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹benzene,2-Q^(b)-5-Q^(s)-6-R¹⁷-4R¹⁸-2-R¹⁹pyridine,3-Q^(b)-6-Q^(s)-2-R¹⁶-5-R¹⁸-R¹⁹pyridine,2-Q^(b)-4-Q^(s)-3-R¹⁶-6-R¹⁸pyrazine,3-Q^(b)-6-Q^(s)-2-R¹⁸-5-R¹⁸-4-R¹⁹pyridazine,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸pyrimidine,5-Q^(b)-2-Q^(s)-3-R¹⁶-6-R¹⁹pyrimidine,3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹thiophene,2-Q^(b)-5-Q^(s)-3-R¹⁶-R¹⁷thiophene, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹furan,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷furan, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹pyrrole,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷pyrrole, 4-Q^(b)-2-Q^(s)-5-R¹⁹imidazole,2-Q^(b)-4-Q^(s)-5-R¹⁷midazole, 3-Q^(b)-5-Q^(s)-4-R¹⁶isoxazole,5-Q^(b)-3-Q^(s)-4isoxazole, 2-Q^(b)-5-Q^(s)-4-R¹⁶pyrazole,4-Q^(b)-2-Q^(s)-5-R¹⁹thiazole, and 2-Q^(b)-5-Q^(s)-4-R¹⁷thiazole; R¹⁶,R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group consistingof hydrido, methyl, ethyl, isopropyl, propyl, carboxy, amidino,guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino,N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio,methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, andcyano; R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no morethan one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b) isQ^(be); Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be)wherein Q^(be) is hydrido, C(NR²⁵)NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),with the provisos that no more than one of R²⁰, R²¹, R²³, and R²⁴ can behydroxy, when any two of the group consisting of R²⁰, R²¹, R²³, and R²⁴are bonded to the same atom and that said Q^(b) group is bonded directlyto a carbon atom; R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independentlyselected from the group consisting of hydrido, methyl, ethyl, propyl,butyl, isopropyl, and hydroxy; Q^(s) is selected from the groupconsisting of a single covalent bond, CH₂, and CH₂CH₂.
 6. The compoundas recited in claim 4 having the Formula:

or a pharmaceutically acceptable salt thereof, wherein; A is selectedfrom the group consisting of CH₂N(CH₃), CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), andCH₂CH₂N(CH₂CH₃); M is selected from the group consisting of N and R¹—C;R¹ is selected from the group consisting of hydrido, hydroxy, amino,amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino,dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl,2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo; R² is Z⁰—Q; Z⁰ isselected from the group consisting of covalent single bond and CH₂; Q isselected from the group consisting of phenyl, 2-thienyl, 3-thienyl,2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl,3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl,2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl,4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and1,3,5triazin-2-yl, wherein a carbon adjacent to the carbon at the pointof attachment is optionally substituted by R⁹, the other carbon adjacentto the carbon at the point of attachment is optionally substituted byR¹³, a carbon adjacent to R⁹ and two atoms from the carbon at the pointof attachment is optionally substituted by R¹⁰, a carbon adjacent to R¹³and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹², and any carbon adjacent to both R¹⁰ and R¹² isoptionally substituted by R¹¹; R⁹, R¹¹, and R¹³ are independentlyselected from the group consisting of hydrido, amidino, guanidino,carboxy, methyl, ethyl, propyl, isopropyl, methoxy, ethoxy, isopropoxy,propoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino, N-ethylamino,methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, and cyano; R¹⁰ and R¹² are independentlyselected from the group consisting of hydrido, amidino, guanidino,carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, fluoro,chloro, bromo, and cyano; Y⁰ is selected from the group consisting of:1-Q^(b)-4-Q^(s)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹benzene,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸-2-R¹⁹pyridine,3-Q^(b)-6-Q^(s)-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine,2-Q^(b)-4-Q^(s)-3-R¹⁶-R¹⁸pyrazine,3-Q^(b)-6-Q^(s)-2-R¹⁸-5-R¹⁸-4-R¹⁹pyridazine,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸pyrimidine,5-Q^(b)-2-Q^(s)-3-R¹⁶-6-R¹⁹pyrimidine,3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹thiophene,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷thiophene, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹furan,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷furan, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹pyrrole,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷pyrrole, 4-Q^(b)-2-Q^(s)-5-R¹⁹imidazole,2-Q^(b)-Q^(s)-5-R¹⁷imidazole, 3-Q^(b)-5-Q^(s)-4-R¹⁶isoxazole,5-Q^(b)-3-Q^(s)-4-R¹⁶isoxazole, 2-Q^(b)-5-Q^(s)-4-R¹⁶pyrazole,4-Q^(b)-2-Q^(s)-5-R¹⁹thiazole, and 2-Q^(b)-5-Q^(s)-4-R¹⁷thiazole; R¹⁶,R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group consistingof hydrido, methyl, ethyl, isopropyl, propyl, amidino, guanidino,methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino, aminomethyl,1-aminoethyl, 2-aminoethyl, N-N-methylamino, dimethylamino,N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio,methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, andcyano; Q^(b) is selected from the group consisting of NR²⁰R²¹,C(NR²⁵)NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the provisos that nomore than one of R²⁰, R²¹, R²³, and R²⁴ can be hydroxy, when any two ofthe group consisting of R²⁰, R²¹, R²³, and R²⁴ are bonded to the sameatom and that said Q^(b) group is bonded directly to a carbon atom; R²⁰,R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selected from the groupconsisting of hydrido, methyl, ethyl, propyl, butyl, isopropyl, andhydroxy; Q^(s) is selected from the group consisting of a singlecovalent bond, CH₂, and CH₂CH₂.
 7. The compound as recited in claim 6 ora pharmaceutically acceptable salt thereof, wherein; A is selected fromthe group consisting of CH₂N(CH₃), CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), andCH₂CH₂N(CH₂CH₃); M is selected from the group consisting of N and R¹—C;R¹ is selected from the group consisting of hydrido, hydroxy, amino,amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl,trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio,trifluoromethoxy, fluoro, and chloro; R² is Z⁰—Q; Z⁰ is selected fromthe group consisting of covalent single bond and CH₂; Q is selected fromthe group consisting of 5-amino-3-amidocarbonylphenyl,5amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl,5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl,3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl,benzyl, 3-carboxyphenyl, 3-carboxy-5-hydroxyphenyl,3-carboxy-5-aminophenyl, 3-chlorophenyl, 2-chlorophenyl, 3-cyanophenyl,3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl, 2-hydroxyphenyl,3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 2-methoxyphenyl,3-methoxyphenyl, 3-methoxyaminophenyl, 3-methoxycarbonylphenyl,2-methylaminophenyl, 3-methylaminophenyl, 2-methylphenyl,3-methylphenyl, 4methylphenyl, phenyl, 3-trifluoroacetamidophenyl,3-trifluoromethylphenyl, 2-trifluoromethylphenyl, 5-amino-2-thienyl,5-amino-3-thienyl, 3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl,and 3-thienyl; Y⁰ is selected from the group consisting of:1-Q^(b)-4-Q^(s)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹benzene,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸-2-R¹⁹pyridine,3-Q^(b)-6-Q^(s)-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine,3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹thiophene, and2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷thiophene; R¹⁶ and R¹⁹ are independentlyselected from the group consisting of hydrido, amidino, amino,aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro,chloro, and cyano; R¹⁶ and R¹⁹ are optionally Q^(b) with the provisothat no more than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and thatQ^(b) is Q^(be); R¹⁷ and R¹⁸ are independently selected from the groupconsisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino,carboxy, and cyano; Q^(b) is selected from the group consisting ofQ^(be) wherein Q^(be) is hydrido and C(NR²⁵)NR²³R²⁴; R²³, R²⁴, and R²⁵are independently selected from the group consisting of hydrido andmethyl; Q^(s) is CH₂.
 8. A compound as recited in claim 7 or apharmaceutically acceptable salt thereof where said compound is selectedfrom the group consisting of:2-[3-[1-[3-aminophenyl]-N-[[4-iminomethylphenyl]methyl]-5-[N,N-dimethylhydrazino]-2,4-dioxo-2(2H,4H)-pyrimidinyl]]acetamide;2-[3-[1-[3-aminophenyl]-5-[N-ethyl-N-methylhydrazino]-N-[[4-iminomethylphenyl]methyl]-2,4-dioxo-2(2H,4H)-pyrimidinyl]]acetamide;2-[3-[1-[3-aminophenyl]-6-fluoro-5-[N,N-diethylhydrazino]-N-[[4-iminomethylphenyl]methyl]-2,4-dioxo-2(2H,4H)-pyrimidinyl]]acetamide;2-[3-[1-[3-aminophenyl]-5-[N-(azetidin-1-yl)amino]-N-[[4-iminomethylphenyl]methyl]-2,4-dioxo-2(2H,4H)-pyrimidinyl]]acetamide;2-[4-[2-[3-aminophenyl]-N-[[4-iminomethylphenyl]methyl]-6-[N,N-dimethylhydrazino]-3,5-dioxo-2(3H,5H)-1,2,4-triazinyl]]acetamide;2-[4-[2-[3-aminophenyl]-6-[N-ethyl-N-methylhydrazino]-N-[[4-iminomethylphenyl]methyl]-3,5-dioxo-2(3H,5H)-1,2,4-triazinyl]]acetamide;2-[4-[2-[3-aminophenyl]-6-[N,N-diethylhydrazino]-N-[[4-iminomethylphenyl]methyl]-3,5-dioxo-2(3H,5H)-1,2,4-triazinyl]]acetamide;2-[4-[2-[3-aminophenyl]-6-[N-(azetidin-1-yl)amino]-N-[[4-iminomethylphenyl]methyl]-3,5-dioxo-2(3H,5H)-1,2,4-triazinyl]]acetamide.9. The compound as recited in claim 2 having the Formula:

or a pharmaceutically acceptable salt thereof, wherein; B is selectedfrom the group consisting of aryl and heteroaryl wherein a carbonadjacent to the carbon at the point of attachment is optionallysubstituted by R³², the other carbon adjacent to the carbon at the pointof attachment is optionally substituted by R³⁶, a carbon adjacent to R³²and two atoms from the carbon at the point of attachment is optionallysubstituted by R³³, a carbon adjacent to R³⁶ and two atoms from thecarbon at the point of attachment is optionally substituted by R³⁵, andany carbon adjacent to both R³³ and R³⁵ is optionally substituted byR³⁴; R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from thegroup consisting of hydrido, acetamido, haloacetamido, amidino,guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino,alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,carboalkoxy, carboxy, carboxamido, cyano, and Q^(b); A is selected fromthe group consisting of single covalent bond and(CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected from 0through 1, pa is an integer selected from 0 through 3, and W⁷ isselected from the group consisting of (R⁷)NC(O) and N(R⁷); R⁷ isselected from the group consisting of hydrido, hydroxy and alkyl; R¹⁵ isselected from the group consisting of hydrido, halo, alkyl andhaloalkyl; M is selected from the group consisting of N and R¹—C; R¹ isselected from the group consisting of hydrido, hydroxy, hydroxyamino,amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino,aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo; R²is Z⁰—Q; Z⁰ is selected from the group consisting of a covalent singlebond, O, S, NH, and CH₂; Q is selected from the group consisting of aryland heteroaryl wherein a carbon adjacent to the carbon at the point ofattachment is optionally substituted by R⁹, the other carbon adjacent tothe carbon at the point of attachment is optionally substituted by R¹³,a carbon adjacent to R⁹ and two atoms from the carbon at the point ofattachment is optionally substituted by R¹⁰, a carbon adjacent to R¹³and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹², and any carbon adjacent to both R¹⁰ and R¹² isoptionally substituted by R¹¹; R⁹, R¹¹, and R¹³ are independentlyselected from the group consisting of hydrido, hydroxy, amino, amidino,guanidino, lower alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl,alkylsulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, alkyl, alkoxy,halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido, andcyano; R¹⁰ and R¹² are independently selected from the group consistingof hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy,hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido,amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl,hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl,amidocarbonyl, halo, haloalkyl, and cyano; Y⁰ is formula (IV):

 wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one is a covalent bond, K² is C, no more than one of D⁵, D⁶,J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵,D⁶, J⁵,and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶ areO and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ are N; R¹⁶, R¹⁷,R¹⁸, and R¹⁹ are independently selected from the group consisting ofhydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy,amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl,alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy,hydroxyalkyl, aminoalkyl, and cyano; R¹⁶ and R¹⁹ are optionally Q^(b)with the proviso that no more than one of R¹⁶ and R¹⁹ is Q^(b) at thesame time and that Q^(b)is Q^(be); Q^(b) is selected from the groupconsisting of NR²⁰R²¹, Q^(be) wherein Q^(be) is hydrido, andC(NR²⁵)NR²³R²⁴, with the provisos that no more than one of R²⁰ and R²¹is hydroxy at the same time and that no more than one of R²³ and R²⁴ ishydroxy at the same time; R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independentlyselected from the group consisting of hydrido, alkyl, and hydroxy; Q^(s)is selected from the group consisting of a single covalent bond, CH₂,and CH₂CH₂.
 10. The compound as recited in claim 9 or a pharmaceuticallyacceptable salt thereof, wherein; B is selected from the groupconsisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl, 3-furyl,2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl, 3-pyrazolyl,4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, 5-isoxazolyl, 2-pyridyl,3-pyridyl, 4-pyridyl, 2-pyrazinyl, 2-pyrimidinyl, 4-pyrimidinyl,5-pyrimidinyl, 3-pyridazinyl, 4-pyridazinyl, and 1,3,5-triazin-2-yl,wherein a carbon adjacent to the carbon at the point of attachment isoptionally substituted by R³², the other carbon adjacent to the carbonat the point of attachment is optionally substituted by R³⁶, a carbonadjacent to R³² and two atoms from the carbon at the point of attachmentis optionally substituted by R³³, a carbon adjacent to R³⁶ and two atomsfrom the carbon at the point of attachment is optionally substituted byR³⁵, and any carbon adjacent to both R³³ and R³⁵ is optionallysubstituted by R³⁴; R³², R³³, R³⁴, R³⁵, and R³⁶ are independentlyselected from the group consisting of hydrido, amidino, guanidino,carboxy, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,methoxyamino, ethoxyamino, acetamido, trifluoroacetamido, N-methylamino,dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, cyano, and Q^(b); A is selected from thegroup consisting of single covalent bond, NH, N(CH₃), N(OH), CH₂, CH₃CH,CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH, C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂,CH₃CHCH₂, and CF₃CHCH₂; M is selected from the group consisting of N andR¹—C; R¹ is selected from the group consisting of hydrido, hydroxy,amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino,dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl,2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo; R² is Z⁰—Q; Z⁰ isselected from the group consisting of a covalent single bond, O, S, NH,and CH₂; Q is selected from the group consisting of phenyl, 2-thienyl,3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl,5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl,2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl,4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a carbon adjacent to thecarbon at the point of attachment is optionally substituted by R⁹, theother carbon adjacent to the carbon at the point of attachment isoptionally substituted by R¹³, a carbon adjacent to R⁹ and two atomsfrom the carbon at the point of attachment is optionally substituted byR¹⁰, a carbon adjacent to R¹³ and two atoms from the carbon at the pointof attachment is optionally substituted by R¹², and any carbon adjacentto both R¹⁰ and R¹² is optionally substituted by R¹¹; R⁹, R¹¹, and R¹³are independently selected from the group consisting of hydrido,amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, N-methylamino,N,N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, and cyano; R¹⁰ and R¹² are independentlyselected from the group consisting of hydrido, amidino, guanidino,carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, fluoro,chloro, bromo, and cyano; Y⁰ is selected from the group consisting of:1-Q^(b)-4-Q^(s)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹benzene,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸-2-R¹⁹pyridine,3-Q^(b)-6-Q^(s)-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine,2-Q^(b)-4-Q^(s)-3-R¹⁶-6-R¹⁸pyrazine,3-Q^(b)-6-Q^(s)-2-R¹⁸-5-R¹⁸-4-R¹⁹pyridazine,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸pyrimidine,5Q^(b)-2-Q^(s)-3-R¹⁶-6-R¹⁹pyrimidine,3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹thiophene,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷thiophene, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹furan,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷furan, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹pyrrole,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷pyrrole, 4-Q^(b)-2-Q^(s)-5-R¹⁹imidazole,2-Q^(b)-4-Q^(s)-5-R¹⁷imidazole, 3-Q^(b)-5-Q^(s)-4-R¹⁶isoxazole,5-Q^(b)-3-Q^(s)-4-R¹⁶isoxazole, 2-Q^(b)-5-Q^(s)-4-R¹⁶pyrazole,4-Q^(b)-2-Q^(s)-5-R¹⁹thiazole, and 2-Q^(b)-5-Q^(s)-4-R¹⁶thiazole; R¹⁶,R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group consistingof hydrido, methyl, ethyl, isopropyl, propyl, carboxy, amidino,guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino,N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio,methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, andcyano; R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no morethan one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b) isQ^(be); Q^(b) is selected from the group consisting of Q^(be) whereinQ^(be) is hydrido and C(NR²⁵)NR²³R²⁴, with the proviso that no more thanone of R²³ and R²⁴ is hydroxy at the same time; R²³, R²⁴, and R²⁵ areindependently selected from the group consisting of hydrido, methyl,ethyl, and hydroxy; Q^(S) is selected from the group consisting of asingle covalent bond, CH₂ and CH₂CH₂.
 11. The compound as recited inclaim 10 or a pharmaceutically acceptable salt thereof, wherein; B isselected from the group consisting of 2-aminophenyl, 3-aminophenyl,3-amidinophenyl, 4-amidinophenyl, 3-carboxyphenyl,3-carboxy-5-hydroxyphenyl, 3-chlorophenyl, 4-chlorophenyl,3,4-dichlorophenyl, 2-fluorophenyl, 3-fluorophenyl, 3,4-difluorophenyl,3-hydroxyphenyl, 4-hydroxyphenyl, 3-methoxyaminophenyl, 3-methoxyphenyl,4-methoxyphenyl, 3-methylphenyl, 4-methylphenyl, phenyl,3-trifluoromethylphenyl, 2-imidazoyl, 2-pyridyl, 3-pyridyl,5-chloro-3-trifluoromethyl-2-pyridyl, 4-pyridyl, 2-thienyl, 3-thienyl,and 3-trifluoromethyl-2-pyridyl; A is selected from the group consistingof CH₂, CH₃CH, CF₃CH, NHC(O), CH₂CH₂, and CH₂CH₂CH₂; M is selected fromthe group consisting of N and R¹—C; R¹ is selected from the groupconsisting of hydrido, hydroxy, amino, amidino, hydroxyamino,aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy,hydroxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro, andchloro; R² is Z⁰—Q; Z⁰ is selected from the group consisting of acovalent single bond, O, S, NH, and CH₂; Q is selected from the groupconsisting of 5-amino-3-amidocarbonylphenyl, 5-amino-2-fluorophenyl,3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl,3-amidinophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl,3-aminophenyl, benzyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl,3-carboxy-5-hydroxyphenyl, 3-carboxymethyl-5-aminophenyl,3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl,2-chlorophenyl, 2,6-dichlorophenyl, 3-cyanophenyl,3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl,2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl,3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl,3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl,phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl,2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl,3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl; Y⁰ isselected from the group consisting of:1-Q^(b)-4-Q^(s)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹benzene,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸-2-R¹⁹pyridine,3-Q^(b)-6-Q^(s)-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine,3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹thiophene, and2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷thiophene; R¹⁶ and R¹⁹ are independentlyselected from the group consisting of hydrido, amidino, amino,aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro,chloro, and cyano; R¹⁶ and R¹⁹ are optionally Q^(b) with the provisothat no more than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and thatQ^(b) is Q^(be); R¹⁷ and R¹⁸ are independently selected from the groupconsisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino,carboxy, and cyano; Q^(b) is selected from the group consisting ofQ^(be) wherein Q^(be) is hydrido and C(NR²⁵)NR²³R²⁴; R²³, R²⁴, and R²⁵are independently selected from the group consisting of hydrido andmethyl; Q^(s) is CH₂.
 12. The compound as recited in claim 9 having theFormula:

or a pharmaceutically acceptable salt thereof, wherein; B is selectedfrom the group consisting of aryl and heteroaryl wherein a carbonadjacent to the carbon at the point of attachment is optionallysubstituted by R³², the other carbon adjacent to the carbon at the pointof attachment is optionally substituted by R³⁶, a carbon adjacent to R³²and two atoms from the carbon at the point of attachment is optionallysubstituted by R³³, a carbon adjacent to R³⁶ and two atoms from thecarbon at the point of attachment is optionally substituted by R³⁵, andany carbon adjacent to both R³³ and R³⁵ is optionally substituted byR³⁴; R³², R³³, R³⁴, R³⁵, and R³⁶ are independently selected from thegroup consisting of hydrido, acetamido, haloacetamido, amidino,guanidino, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino,alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,carboalkoxy, carboxy, carboxamido, cyano, and Q^(b); A is selected fromthe group consisting of single covalent bond and(CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected from 0through 1, pa is an integer selected from 0 through 3, and W⁷ is N(R⁷);R⁷ is selected from the group consisting of hydrido and alkyl; R¹⁵ isselected from the group consisting of hydrido, halo, alkyl, andhaloalkyl; M is selected from the group consisting of N and R¹—C; R¹ isselected from the group consisting of hydrido, hydroxy, hydroxyamino,amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino,aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo; R²is Z⁰—Q; Z⁰ is a covalent single bond; Q is selected from the groupconsisting of aryl and heteroaryl wherein a carbon adjacent to thecarbon at the point of attachment is optionally substituted by R⁹, theother carbon adjacent to the carbon at the point of attachment isoptionally substituted by R¹³, a carbon adjacent to R⁹ and two atomsfrom the carbon at the point of attachment is optionally substituted byR¹⁰, a carbon adjacent to R¹³ and two atoms from the carbon at the pointof attachment is optionally substituted by R¹², and any carbon adjacentto both R¹⁰ and R¹² is optionally substituted by R¹¹; R⁹, R¹¹, and R¹³are independently selected from the group consisting of hydrido,hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkoxy,alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkylamidosulfonyl,alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido,and cyano; R¹⁰ and R¹² are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, amidino, guanidino,alkyl, alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, loweralkylamino, alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl,dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl,carboalkoxy, carboxy, carboxyamido, carboxyalkyl, and cyano; Y⁰ isformula (IV):

 wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one is a covalent bond, K² is C, no more than one of D⁵, D⁶,J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵,D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ are N; R¹⁶,R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group consistingof hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy,amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl,alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy,hydroxyalkyl, aminoalkyl, and cyano; R¹⁶ and R¹⁹ are optionally Q withthe proviso that no more than one of R¹⁶ and R¹⁹ is Q^(b) at the sametime and that Q^(b) is Q^(be); Q^(b) is selected from the groupconsisting of NR²⁰R²¹, Q^(be) wherein Q^(be) is hydrido, andC(NR²⁵)NR²³R²⁴; R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selectedfrom the group consisting of hydrido and alkyl; Q^(s) is CH₂.
 13. Thecompound as recited in claim 12 or a pharmaceutically acceptable saltthereof, wherein; B is selected from the group consisting of phenyl,2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl,2-imidazolyl, 4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl,3-isoxazolyl, and 5-isoxazolyl, wherein a carbon adjacent to the carbonat the point of attachment is optionally substituted by R³², the othercarbon adjacent to the carbon at the point of attachment is optionallysubstituted by R³⁶, a carbon adjacent to R³² and two atoms from thecarbon at the point of attachment is optionally substituted by R³³, acarbon adjacent to R³⁶ and two atoms from the carbon at the point ofattachment is optionally substituted by R³⁵, and any carbon adjacent toboth R³³ and R³⁵ is optionally substituted by R³⁴; R³², R³³, R³⁴, R³⁵,and R³⁶ are independently selected from the group consisting of hydrido,amidino, guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, amino,N-methylamino, dimethylamino, methylthio, ethylthio, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo,amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl,carboxy, cyano, and Q^(b); A is selected from the group consisting ofsingle covalent bond, NH, N(CH₃), CH₂, CH₃CH, and CH₂CH₂; M is selectedfrom the group consisting of N and R¹—C; R¹ is selected from the groupconsisting of hydrido, hydroxy, amino, amidino, hydroxyamino,aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy,hydroxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro, andchloro; R² is selected from the group consisting of phenyl, 2-thienyl,2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl,and 3-pyridyl, wherein a carbon adjacent to the carbon at the point ofattachment is optionally substituted by R⁹, the other carbon adjacent tothe carbon at the point of attachment is optionally substituted by R¹³,a carbon adjacent to R⁹ and two atoms from the carbon at the point ofattachment is optionally substituted by R¹⁰, a carbon adjacent to R¹³and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹², and any carbon adjacent to both R¹⁰ and R¹² isoptionally substituted by R¹¹; R⁹, R¹¹, and R¹³ are independentlyselected from the group consisting of hydrido, methyl, ethyl, methoxy,ethoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino, methylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro,bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,carboxy, and cyano; R¹⁰ and R¹² are independently selected from thegroup consisting of hydrido, amidino, amidocarbonyl,N-methylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy,hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxy,carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, trifluoroacetamido, aminomethyl, N-methylamino,dimethylamino, amidosulfonyl, N-methylamidosulfonyl,N,N-dimethylamidosulfonyl, methoxycarbonyl, fluoro, chloro, bromo, andcyano; Y⁰ is selected from the group consisting of:1-Q^(b)-4-Q^(s)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹benzene,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸-2-R¹⁹pyridine,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷thiophene,3-Q^(b)-6-Q^(s)-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine,3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹thiophene, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹furan,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷furan, 3-Q^(b)-5-Q^(s)-4R¹⁶-2-R¹⁹pyrrole,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷pyrrole, 4-Q^(b)-2-Q^(s)-5-R¹⁹thiazole, and2-Q^(b)-5-Q^(s)-4-R¹⁷thiazole; R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independentlyselected from the group consisting of hydrido, methyl, ethyl, amidino,guanidino, methoxy, hydroxy, amino, aminomethyl, 1-aminoethyl,2-aminoethyl, N-methylamino, dimethylamino, methylthio, ethylthio,trifluoromethylthio, methylsulfinyl, methylsulfonyl, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoromethoxy, fluoro,chloro, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, carboxy,and cyano. Q^(b) is selected from the group consisting of NR²⁰R²¹ andC(NR²⁵)NR²³R²⁴, with the proviso that said Q^(b) group is bondeddirectly to a carbon atom; R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independentlyselected from the group consisting of hydrido, methyl, and ethyl; Q^(s)is CH₂.
 14. The compound as recited in claim 13 or a pharmaceuticallyacceptable salt thereof, wherein; B is selected from the groupconsisting of 2-aminophenyl, 3-aminophenyl, 3-amidinophenyl,4-amidinophenyl, 3-carboxyphenyl, 3-carboxy-5-hydroxyphenyl,3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 2-fluorophenyl,3-fluorophenyl, 3,4-difluorophenyl, 3-hydroxyphenyl, 4-hydroxyphenyl,3-methoxyaminophenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3-methylphenyl,4-methylphenyl, phenyl, 3-trifluoromethylphenyl, 2-imidazoyl, 2-pyridyl,3-pyridyl, 5-chloro-3-trifluoromethyl-2-pyridyl, 4-pyridyl, 2-thienyl,3-thienyl, and 3-trifluoromethyl-2-pyridyl; A is selected from the groupconsisting of CH₂, CH₃CH, CF₃CH, NHC(O), CH₂CH₂, and CH₂CH₂CH₂; M isselected from the group consisting of N and R¹—C; R¹ is selected fromthe group consisting of hydrido, hydroxy, amino, methyl,trifluoromethyl, fluoro, and chloro; R² is selected from the groupconsisting of 5-amino-3-amidocarbonylphenyl, 5-amino-2-fluorophenyl,3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl,3-amidinophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl,3-aminophenyl, benzyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl,3-carboxy-5-hydroxyphenyl, 3-carboxymethyl-5-aminophenyl,3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl,2-chlorophenyl, 3-cyanophenyl, 3-dimethylaminophenyl, 2-fluorophenyl,3-fluorophenyl, 2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl,3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl,3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl,phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl,2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl,3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl; Y⁰ isselected from the group consisting of:1-Q^(b)-4-Q^(s)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹benzene,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸-2-R¹⁹pyridine,3-Q^(b)-6-Q^(s)-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine,3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹thiophene, and2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷thiophene; R¹⁶ and R¹⁹ are independentlyselected from the group consisting of hydrido, amidino, amino,aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro,chloro, and cyano; R¹⁶ and R¹⁹ are optionally Q^(b) with the provisothat no more than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and thatQ^(b) is Q^(be); R¹⁷ and R¹⁸ are independently selected from the groupconsisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino,carboxy, and cyano; Q^(b) is selected from the group consisting ofQ^(be) wherein Q^(be) is hydrido and C(NR²⁵)NR²³R²⁴; R²³, R²⁴, and R²⁵are independently selected from the group consisting of hydrido andmethyl; Q^(s) is CH₂.
 15. The compound as recited in claim 14 or apharmaceutically acceptable salt thereof, wherein; B is selected fromthe group consisting of 3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl,3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 2-fluorophenyl,4-methylphenyl, phenyl, 2-imidazoyl, 3-pyridyl, 4-pyridyl, and3-trifluoromethyl-2-pyridyl; A is selected from the group consisting ofCH₂, NHC(O), CH₂CH₂, and CH₂CH₂CH₂; M is selected from the groupconsisting of N and R¹—C; R¹ is selected from the group consisting ofhydrido, fluoro, and chloro; R² is selected from the group consisting of3-aminophenyl, benzyl, 3-chlorophenyl, 3-dimethylaminophenyl,3-hydroxyphenyl, 3-methanesulfonylaminophenyl, 3-methylaminophenyl,2-methylphenyl, 3-methylphenyl, phenyl, 3-trifluoroacetamidophenyl,3-bromo-2-thienyl, 2-thienyl, and 3-thienyl; Y⁰ is selected from thegroup consisting of 5-amidino-2-thienylmethyl, 4-amidinobenzyl,2-fluoro-4-amidinobenzyl, and 3-fluoro-4-amdinobenzyl.
 16. A compound asrecited in claim 9 where said compound is selected from the group havingthe Formula:

or a pharmaceutically acceptable salt thereof, wherein: R² is3-aminophenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl,and M is CH; R² is 3-aminophenyl, B is phenyl, A is CH₂, Y⁰ is4-amidinobenzyl, and M is CH; R² is phenyl, B is 3-chlorophenyl, A isCH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CH; R² is 3-aminophenyl, B is2-imidazoyl, A is CH₂CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CH; R² is3-dimethylaminophenyl, B is phenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl,and M is CH; R² is 2-methylphenyl, B is phenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, and M is CH; R² is phenyl, B is 3-aminophenyl, A isC(O)NH, Y⁰ is 4-amidinobenzyl, and M is CH; R² is phenyl, B is3-amidinophenyl, A is CH₂, Y⁰ is 4-amidinobenzyl, and M is CH; R² is3-(N-methylamino)phenyl, B is phenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, and M is CH; R² is 3-thienyl, B is phenyl, A is CH₂CH₂,Y⁰ is 4-amidinobenzyl, and M is CH; R² is 3-methylsulfonamidophenyl, Bis phenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CH; R² isphenyl, B is 4-amidinophenyl, A is CH₂, Y⁰ is 4-amidinobenzyl, and M isCH; R² is 3-methylaminophenyl, B is phenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, and M is CH; R² is phenyl, B is phenyl, A is CH₂, Y⁰ is4-amidinobenzyl, and M is CH; R² is phenyl, B is 4-pyridyl, A is CH₂CH₂,Y⁰ is 4-amidinobenzyl, and M is CH; R² is phenyl, B is 3-pyridyl, A isCH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CH; R² is 3-chlorophenyl, B is4-pyridyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CH; R² is3-methylphenyl, B is 4-phenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and Mis CH; R² is 3-thienyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, and M is CH; R² is 3-aminophenyl, B is 3-chlorophenyl,A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CF; R² is 3-aminophenyl, Bis phenyl, A is CH₂, Y⁰ is 4-amidinobenzyl, and M is CF; R² is phenyl, Bis 3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CF; R²is 3-aminophenyl, B is 2-imidazoyl, A is CH₂CH₂CH₂, Y⁰ is4-amidinobenzyl, and M is CF; R² is 3-dimethylaminophenyl, B is phenyl,A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CF; R² is 2-methylphenyl, Bis phenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CF; R² isphenyl, B is 3-aminophenyl, A is C(O)NH, Y⁰ is 4-amidinobenzyl, and M isCF; R² is phenyl, B is 3-amidinophenyl, A is CH₂, Y⁰ is 4-amidinobenzyl,and M is CF; R² is 3-(N-methylamino)phenyl, B is phenyl, A is CH₂CH₂, Y⁰is 4-amidinobenzyl, and M is CF; R² is 3-thienyl, B is phenyl, A isCH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CF; R² is3-methylsulfonamidophenyl, B is phenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, and M is CF; R² is phenyl, B is 4-amidinophenyl, A isCH₂, Y⁰ is 4-amidinobenzyl, and M is CF; R² is 3-methylaminophenyl, B isphenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CF; R² is phenyl, Bis phenyl, A is CH₂, Y⁰ is 4-amidinobenzyl, and M is CF; R² is phenyl, Bis 4-pyridyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CF; R² isphenyl, B is 3-pyridyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CF;R² is 3-chlorophenyl, B is 4-pyridyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, and M is CF; R² is 3-methylphenyl, B is 4-phenyl, A isCH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CF; R² is 3-thienyl, B is3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CF; R² is3-aminophenyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl,and M is N; R² is 3-aminophenyl, B is phenyl, A is CH₂, Y⁰ is4-amidinobenzyl, and M is N; R² is phenyl, B is 3-chlorophenyl, A isCH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is N; R² is 3-aminophenyl, B is2-imidazoyl, A is CH₂CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is N; R² is3-dimethylaminophenyl, B is phenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl,and M is N; R² is 2-methylphenyl, B is phenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, and M is N; R² is phenyl, B is 3-aminophenyl, A isC(O)NH, Y⁰ is 4-amidinobenzyl, and M is N; R² is phenyl, B is3-amidinophenyl, A is CH₂, Y⁰ is 4-amidinobenzyl, and M is N; R² is3-(N-methylamino)phenyl, B is phenyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, and M is N; R² is 3-thienyl, B is phenyl, A is CH₂CH₂,Y⁰ is 4-amidinobenzyl, and M is N; R² is 3-methylsulfonamidophenyl, B isphenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is N; R² is phenyl, Bis 4-amidinophenyl, A is CH₂, Y⁰ is 4-amidinobenzyl, and M is N; R² is3-methylaminophenyl, B is phenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl,and M is N; R² is phenyl, B is phenyl, A is CH₂, Y⁰ is 4-amidinobenzyl,and M is N; R² is phenyl, B is 4-pyridyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, and M is N; R² is phenyl, B is 3-pyridyl, A is CH₂CH₂,Y⁰ is 4-amidinobenzyl, and M is N; R² is 3-chlorophenyl, B is 4-pyridyl,A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is N; R² is 3-methylphenyl, Bis 4-phenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is N; R² is3-thienyl, B is 3-chlorophenyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, andM is N.
 17. The compound as recited in claim 2 having the Formula:

or a pharmaceutically acceptable salt thereof, wherein; B is selectedfrom the group consisting of hydrido, C2-C8 alkyl, C3-C8 alkenyl, C3-C8alkynyl, and C2-C8 haloalkyl, wherein each member of group B isoptionally substituted at any carbon up to and including 6 atoms fromthe point of attachment of B to A with one or more of the groupconsisting of R³², R³³, R³⁴, R³⁵, and R³⁶; R³², R³³, R³⁴, R³⁵, and R³⁶are independently selected from the group consisting of hydrido,acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino,alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkylamidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, andQ^(b); A is selected from the group consisting of single covalent bondand (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected from 0through 1, pa is an integer selected from 0 through 3, and W⁷ isselected from the group consisting of (R⁷)NC(O) and N(R⁷); R⁷ isselected from the group consisting of hydrido, hydroxy and alkyl; R¹⁵ isselected from the group consisting of hydrido, halo, alkyl, andhaloalkyl; M is selected from the group consisting of N and R¹—C; R¹ isselected from the group consisting of hydrido, hydroxy, hydroxyamino,amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino,aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo; R²is Z⁰—Q; Z⁰ is selected from the group consisting of a covalent singlebond, O, S, NH, and CH₂; Q is selected from the group consisting of aryland heteroaryl wherein a carbon adjacent to the carbon at the point ofattachment is optionally substituted by R⁹, the other carbon adjacent tothe carbon at the point of attachment is optionally substituted by R¹³,a carbon adjacent to R⁹ and two atoms from the carbon at the point ofattachment is optionally substituted by R¹⁰, a carbon adjacent to R¹³and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹², and any carbon adjacent to both R¹⁰ and R¹² isoptionally substituted by R¹¹; R⁹, R¹¹, and R¹³ are independentlyselected from the group consisting of hydrido, hydroxy, amino, amidino,guanidino, lower alkylamino, alkylthio, alkylsulfonamido, alkylsulfinyl,alkylsulfonyl, amidosulfonyl, monoalkyl amidosulfonyl, alkyl, alkoxy,halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido, andcyano; R¹⁰ and R¹² are independently selected from the group consistingof hydrido, acetamido, haloacetamido, amidino, guanidino, alkyl, alkoxy,hydroxy, amino, alkoxyamino, lower alkylamino, alkylsulfonamido,amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl,hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy, carboxyalkyl,amidocarbonyl, halo, haloalkyl, and cyano; Y⁰ is formula (IV):

 wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one is a covalent bond, K² is C, no more than one of D⁵, D⁶,J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵,D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ are N; R¹⁶,R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group consistingof hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy,amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl,alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy,hydroxyalkyl, aminoalkyl, and cyano; R¹⁶ and R¹⁹ are optionally Q^(b)with the proviso that no more than one of R¹⁶ and R¹⁹ is Q^(b) at thesame time and that Q^(b) is Q^(be); Q^(b) is selected from the groupconsisting of NR²⁰R²¹, Q^(be) wherein Q^(be) is hydrido, C(NR²⁵)NR²³R²⁴,and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the provisos that no more than one ofR²⁰ and R²¹ is hydroxy at the same time and that no more than one of R²³and R²⁴ is hydroxy at the same time; R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶are independently selected from the group consisting of hydrido, alkyl,and hydroxy; Q^(s) is selected from the group consisting of a singlecovalent bond, CH₂, and CH₂CH₂.
 18. The compound as recited in claim 17or a pharmaceutically acceptable salt thereof, wherein; B is selectedfrom the group consisting of hydrido, ethyl, 2-propynyl, 2-propenyl,propyl, isopropyl, butyl, 2-butenyl, 3-butenyl, 2-butynyl, sec-butyl,tert-butyl, isobutyl, 2-methylpropenyl, 1-pentyl, 2-pentenyl,3-pentenyl, 4-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl,1-methyl-2-butenyl, 1-methyl-3-butenyl, 1-methyl-2-butynyl, 3-pentyl,1-ethyl-2-propenyl, 2-methylbutyl, 2-methyl-2-butenyl,2-methyl-3-butenyl, 2-methyl-3-butynyl, 3-methylbutyl,3-methyl-2-butenyl, 3-methyl-3-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl,4-hexenyl, 5-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl,1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-4-pentenyl,1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl,1-ethyl-3-butenyl, 1-propyl-2-propenyl, 1-ethyl-2-butynyl, 1-heptyl,2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl, 2-heptynyl,3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl,1-methyl-3-hexenyl, 1-methyl4-hexenyl, 1-methyl-5hexenyl,1-methyl-2-hexynyl, 1-methyl-3-hexynyl, 1-methyl-4-hexynyl, 3-heptyl,1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl, 1-ethyl-4-pentenyl,1-butyl-2-propenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl,2,2,2-trifluoroethyl, 2,2-difluoropropyl,4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl,5,5,6,6,6-pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein eachmember of group B is optionally substituted at any carbon up to andincluding 5 atoms from the point of attachment of B to A with one ormore of the group consisting of R³², R³³, R³⁴, R³⁵, and R³⁶; R³², R³³,R³⁴, R³⁵, and R³⁶ are independently selected from the group consistingof hydrido, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy,propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido,trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino,methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, cyano, and Q^(b); A is selected from thegroup consisting of single covalent bond, NH, N(CH₃), N(OH), CH₂, CH₃CH,CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH, C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂,CH₃CHCH₂, and CF₃CHCH₂; M is selected from the group consisting of N andR¹—C; R¹ is selected from the group consisting of hydrido, hydroxy,amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino,dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl,2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo; R² is Z⁰—Q; Z⁰ isselected from the group consisting of a covalent single bond, O, S, NH,and CH₂; Q is selected from the group consisting of phenyl, 2-thienyl,3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl,5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl,2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl,4-pyridazinyl, and 1,3,5triazin-2-yl, wherein a carbon adjacent to thecarbon at the point of attachment is optionally substituted by R⁹, theother carbon adjacent to the carbon at the point of attachment isoptionally substituted by R¹³, a carbon adjacent to R⁹ and two atomsfrom the carbon at the point of attachment is optionally substituted byR¹⁰, a carbon adjacent to R¹³ and two atoms from the carbon at the pointof attachment is optionally substituted by R¹², and any carbon adjacentto both R¹⁰ and R¹² is optionally substituted by R¹¹; R⁹, R¹¹, and R¹³are independently selected from the group consisting of hydrido,amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, N-methylamino,N,N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, and cyano; R¹⁰ and R¹² are independentlyselected from the group consisting of hydrido, amidino, guanidino,carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, fluoro,chloro, bromo, and cyano; Y⁰ is selected from the group consisting of:1-Q^(b)-4-Q^(s)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹benzene,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸-2-R¹⁹pyridine,3-Q^(b)-6-Q^(s)-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine,2-Q^(b)-4-Q^(s)-3-R¹⁶-6-R¹⁸pyrazine,3-Q^(b)-6-Q^(s)-2-R¹⁸-5-R¹⁸-4-R¹⁹pyridazine,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸pyrimidine,5-Q^(b)-2-Q^(s)-3-R¹⁶-6-R¹⁹pyrimidine,3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹thiophene,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷thiophene, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹furan,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷furan, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹pyrrole,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷pyrrole, 4-Q^(b)-2-Q^(s)-5-R¹⁹imidazole,2-Q^(b)-4-Q^(s)-5-R¹⁷imidazole, 3-Q^(b)-5-Q^(s)-4-R¹⁶isoxazole,5-Q^(b)-3-Q^(s)-4-R¹⁶isoxazole, 2-Q^(b)-5-Q^(s)-4-R¹⁶pyrazole,4-Q^(b)-2-Q^(s)-5-R¹⁹thiazole, and 2-Q^(b)-5-Q^(s)-4-R¹⁷thiazole; R¹⁶,R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group consistingof hydrido, methyl, ethyl, isopropyl, propyl, carboxy, amidino,guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino,N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio,methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, andcyano; R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no morethan one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b) isQ^(be); Q^(b) is selected from the group consisting of NR²⁰R²¹, Q^(be),wherein Q^(be) is hydrido, C(N²⁵NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴),with the provisos that no more than one of R²⁰ and R²¹ is hydroxy at thesame time and that no more than one of R²³ and R²⁴ is hydroxy at thesame time; R²⁰, R²¹, R²³, R²⁴, R²⁵, and R²⁶ are independently selectedfrom the group consisting of hydrido, methyl, ethyl, propyl, butyl,isopropyl, and hydroxy; Q^(s) is selected from the group consisting of asingle covalent bond, CH₂, and CH₂CH₂.
 19. The compound as recited inclaim 18 or a pharmaceutically acceptable salt thereof, wherein; B isselected from the group consisting of hydrido,ethyl, 2-propenyl,2-propynyl, propyl, isopropyl, butyl, 2-butyl, (R)-2-butyl,(S)-2-butyl,tert-butyl, isobutyl, 1-pentyl, 3-pentyl, 2-methylbutyl,2,2,2-trifluoroethyl, 6-amidocarbonylhexyl, 4-methyl-2-pentyl,3-hydroxypropyl, 3-methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl,3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl,2-hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl,4-guanidinobutyl, 3-hydroxypropyl, 4hydroxybutyl, 6-cyanohexyl,2-dimethylaminoethyl, 3-methylbutyl, 2-methylbutyl, (S)-2-methylbutyl,3-aminopropyl, 2-hexyl, and 4-aminobutyl; A is selected from the groupconsisting of single covalent bond,CH₂, NHC(O), CH₂CH₂, CH₂CH₂CH₂, andCH₃CHCH₂; M is selected from the group consisting of N and R¹—C; R¹ isselected from the group consisting of hydrido, hydroxy, amino, amidino,hydroxyamino, aminomethyl, methylamino, cyano, methyl, trifluoromethyl,methoxy, hydroxymethyl, methoxyamino, methylthio, trifluoromethoxy,fluoro, and chloro; R² is Z⁰—Q; Z⁰ is selected from the group consistingof a covalent single bond, O, S, NH, and CH₂; Q is selected from thegroup consisting of 5-amino-3-amidocarbonylphenyl,5amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl,5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl,3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl,benzyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl,3-carboxy-5-hydroxyphenyl, 3-carboxymethyl-5-aminophenyl,3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl,2-chlorophenyl, 2,6-dichlorophenyl, 3-cyanophenyl,3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl,2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl,3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl,3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl,phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl,2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl,3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl; Y⁰ isselected from the group consisting of:1-Q^(b)-4Q^(s)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹benzene,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸-2-R¹⁹pyridine, 3-Q^(b)-6-Q^(s)-2-R¹⁶-5R¹⁸-4R¹⁹pyridine, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹thiophene, and2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷thiophene; R¹⁶ and R¹⁹ are independentlyselected from the group consisting of hydrido, amidino, amino,aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro,chloro, and cyano; R¹⁶ and R¹⁹ are optionally Q^(b) with the provisothat no more than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and thatQ^(b) is Q^(be); R¹⁷ and R¹⁸ are independently selected from the groupconsisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino,carboxy, and cyano; Q^(b) is selected from the group consisting ofQ^(be) wherein Q^(be) is hydrido and C(NR²⁵)NR²³R²⁴; R²³, R²⁴, and R²⁵are independently selected from the group consisting of hydrido andmethyl; Q^(s)is CH₂.
 20. The compound as recited in claim 17 having theFormula:

or a pharmaceutically acceptable salt therof, wherein; B is selectedfrom the group consisting of hydrido, C2-C8 alkyl, C3-C8 alkenyl, C3-C8alkynyl, and C2-C8 haloalkyl, wherein each member of group B isoptionally substituted at any carbon up to and including 6 atoms fromthe point of attachment of B to A with one or more of the groupconsisting of R³², R³³, R³⁴, R³⁵, and R³⁶; R³², R³³, R³⁴, R³⁵, and R³⁶are independently selected from the group consisting of hydrido,acetamido, haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino,alkoxyamino, lower alkylamino, alkylthio, amidosulfonyl, monoalkylamidosulfonyl, dialkyl amidosulfonyl, alkyl, halo, haloalkyl,haloalkoxy, hydroxyalkyl, carboalkoxy, carboxy, carboxamido, cyano, andQ^(b); A is selected from the group consisting of single covalent bondand (CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected from 0through 1, pa is an integer selected from 0 through 3, and W⁷ is N(R⁷);R⁷ is selected from the group consisting of hydrido and alkyl; R¹⁵ isselected from the group consisting of hydrido, halo, alkyl, andhaloalkyl; M is selected from the group consisting of N and R¹—C; R¹ isselected from the group consisting of hydrido, hydroxy, hydroxyamino,amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino,aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo; R²is Z⁰—Q; Z⁰ is a covalent single bond; Q is selected from the groupconsisting of aryl and heteroaryl wherein a carbon adjacent to thecarbon at the point of attachment is optionally substituted by R⁹, theother carbon adjacent to the carbon at the point of attachment isoptionally substituted by R¹³, a carbon adjacent to R⁹ and two atomsfrom the carbon at the point of attachment is optionally substituted byR¹⁰, a carbon adjacent to R¹³ and two atoms from the carbon at the pointof attachment is optionally substituted by R¹², and any carbon adjacentto both R¹⁰ and R¹² is optionally substituted by R¹¹; R⁹, R¹¹, and R¹³are independently selected from the group consisting of hydrido,hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkoxy,alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkylamidosulfonyl,alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido,and cyano; R¹⁰ and R¹² are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, amidino, guanidino,alkyl, alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, loweralkylamino, alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl,dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl,carboalkoxy, carboxy, carboxyamido, carboxyalkyl, and cyano; Y⁰ isformula (IV):

 wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one is a covalent bond, K² is C, no more than one of D⁵, D⁵,J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵,D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ are N; R¹⁶,R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group consistingof hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy,amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl,alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy,hydroxyalkyl, aminoalkyl, and cyano; R¹⁶ and R¹⁹ are optionally Q^(b)with the proviso that no more than one of R¹⁶ and R¹⁹ is Q^(b) at thesame time and that Q^(b) is Q^(be); Q^(b) is selected from the groupconsisting of NR²⁰R²¹, Q^(be) wherein Q^(be) is hydrido,N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴; R²⁰, R²¹, R²³, R²⁴, R²⁵,and R²⁶ are independently selected from the group consisting of hydridoand alkyl; Q^(s) is CH₂.
 21. The compound as recited in claim 17 or apharmaceutically acceptable salt thereof, wherein; B is selected fromthe group consisting of hydrido, ethyl, 2-propenyl, 2-propynyl, propyl,isopropyl, butyl, 2-butenyl, 2-butynyl, sec-butyl, tert-butyl, isobutyl,2-methylpropenyl, 1-pentyl, 2-pentenyl, 3-pentenyl, 2-pentynyl,3-pentynyl, 2-pentyl, 3-pentyl, 2-methylbutyl, 2-methyl-2-butenyl,3-methylbutyl, 3-methyl-2-butenyl, 1-hexyl, 2-hexenyl, 3-hexenyl,4-hexenyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 2-hexyl,1-methyl-2-pentenyl, 1-methyl-3-pentenyl, 1-methyl-2-pentynyl,1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl, 1-heptyl, 2-heptenyl,3-heptenyl, 4-heptenyl, 5-heptenyl, 2-heptynyl, 3-heptynyl, 4-heptynyl,5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl, 1-methyl-3-hexenyl,1-methyl-4-hexenyl, 1-methyl-2-hexynyl, 1-methyl-3-hexynyl,1-methyl-4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl, 1-ethyl-3-pentenyl,1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl, 2,2,2-trifluoroethyl,2,2-difluoropropyl, 4-trifluoromethyl-5,5,5-trifluoropentyl,4-trifluoromethylpentyl, 5,5,6,6,6-pentafluorohexyl, and3,3,3-trifluoropropyl, wherein each member of group B is optionallysubstituted at any carbon up to and including 5 atoms from the point ofattachment of B to A with one or more of the group consisting of R³²,R³³, R³⁴, R³⁵, and R³⁶; R³², R³³, R³⁴, R³⁵, and R³⁶ are independentlyselected from the group consisting of hydrido, amidino, guanidino,methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino,dimethylamino, methylthio, ethylthio, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, carboxy, cyano, andQ^(b); A is selected from the group consisting of single covalent bond,NH, N(CH₃), CH₂, CH₃CH, and CH₂CH₂; A is optionally selected from thegroup consisting of CH₂N(CH₃), CH₂N(CH₂CH₃), CH₂CH₂N(CH₃), andCH₂CH₂N(CH₂CH₃) with the proviso that B is hydrido; M is selected fromthe group consisting of N and R¹—C; R¹ is selected from the groupconsisting of hydrido, hydroxy, amino, amidino, hydroxyamino,aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy,hydroxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro, andchloro; R² is selected from the group consisting of phenyl, 2-thienyl,2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl,and 3-pyridyl, wherein a carbon adjacent to the carbon at the point ofattachment is optionally substituted by R⁹, the other carbon adjacent tothe carbon at the point of attachment is optionally substituted by R¹³,a carbon adjacent to R⁹ and two atoms from the carbon at the point ofattachment is optionally substituted by R¹⁰, a carbon adjacent to R¹³and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹², and any carbon adjacent to both R¹⁰ and R¹² isoptionally substituted by R¹¹; R⁹, R¹¹, and R¹³ are independentlyselected from the group consisting of hydrido, methyl, ethyl, methoxy,ethoxy, hydroxy, amino, N-methylamino, N,N-dimethylamino, methylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro,bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,carboxy, and cyano; R¹⁰ and R¹² are independently selected from thegroup consisting of hydrido, amidino, amidocarbonyl,N-methylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy,hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxy,carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, trifluoroacetamido, aminomethyl, N-methylamino,dimethylamino, amidosulfonyl, N-methylamidosulfonyl,N,N-dimethylamidosulfonyl, methoxycarbonyl, fluoro, chloro, bromo, andcyano; Y⁰ is selected from the group consisting of:1-Q^(b)-4-Q^(s)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹benzene,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸-2-R¹⁹pyridine,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷thiophene,3-Q^(b)-6-Q^(s)-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine,3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹thiophene, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹furan,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷furan, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹pyrrole,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷pyrrole, 4-Q^(b)-2-Q^(s)-5-R¹⁹thiazole, and2-Q^(b)-5-Q^(s)-4R¹⁷thiazole; R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independentlyselected from the group consisting of hydrido, methyl, ethyl, amidino,guanidino, methoxy, hydroxy, amino, aminomethyl, 1-aminoethyl,2-aminoethyl, N-methylamino, dimethylamino, methylthio, ethylthio,trifluoromethylthio, methylsulfinyl, methylsulfonyl, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, trifluoromethoxy, fluoro,chloro, amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, carboxy,and cyano. Q^(b) is selected from the group consisting of NR²⁰R²¹;C(NR²⁵)NR²³R²⁴, and N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), with the proviso that saidQ^(b) group is bonded directly to a carbon atom; R²⁰, R²¹, R²³, R²⁴,R²⁵, and R²⁶ are independently selected from the group consisting ofhydrido, methyl, and ethyl; Q^(s) is CH₂.
 22. The compound as recited inclaim 21 or a pharmaceutically acceptable salt thereof, wherein; B isselected from the group consisting of hydrido,ethyl, 2-propenyl,2-propynyl, propyl, isopropyl, butyl, 2-butyl, (R)-2-butyl,(S)-2-butyl,tert-butyl, isobutyl, 1-pentyl, 3-pentyl, 2-methylbutyl,2,2,2-trifluoroethyl, 6-amidocarbonylhexyl, 4-methyl-2-pentyl,3-hydroxypropyl, 3-methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl,3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl,2-hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl,4-guanidinobutyl, 3-hydroxypropyl, 4-hydroxybutyl, 6-cyanohexyl,2-dimethylaminoethyl, 3-methylbutyl, 2-methylbutyl, (S)-2-methylbutyl,3-aminopropyl, 2-hexyl, and 4-aminobutyl; A is selected from the groupconsisting of single covalent bond, CH₂, CH₃CH, and CH₂CH₂; M isselected from the group consisting of N and R¹—C; R¹ is selected fromthe group consisting of hydrido, hydroxy, amino, methyl,trifluoromethyl, fluoro, and chloro; R² is selected from the groupconsisting of 5-amino-3-amidocarbonylphenyl, 5-amino-2-fluorophenyl,3-amino-5-hydroxymethylphenyl, 5-amino-3-methoxycarbonylphenyl,3-amidinophenyl, 3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl,3-aminophenyl, benzyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl,3-carboxy-5-hydroxyphenyl, 3-carboxymethyl-5-aminophenyl,3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl,2-chlorophenyl, 2,6-dichlorophenyl, 3-cyanophenyl,3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl,2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl,3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl,3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl,phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl,2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl,3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl; Y⁰ isselected from the group consisting of:1-Q^(b)-4-Q^(s)-2-R¹⁶-3-R¹⁷-R¹⁸-6-R¹⁹benzene,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸-2-R¹⁹pyridine,3-Q^(b)-6-Q^(s)-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine,3-Q^(b)-5-Q^(s)-2-R¹⁹thiophene, and2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷thiophene; R¹⁶ and R¹⁹ are independentlyselected from the group consisting of hydrido, amidino, amino,aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro,chloro, and cyano; R¹⁶ and R¹⁹ are optionally Q^(b) with the provisothat no more than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and thatQ^(b) is Q^(be); R¹⁷ and R¹⁸ are independently selected from the groupconsisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino,carboxy, and cyano; Q^(b) is selected from the group consisting ofQ^(be) wherein Q^(be) is hydrido and C(NR²⁵)NR²³R²⁴; R²³, R²⁴, and R²⁵are independently selected from the group consisting of hydrido andmethyl; Q^(s) is CH₂.
 23. The compound as recited in claim 22 or apharmaceutically acceptable salt thereof, wherein; B is selected fromthe group consisting of hydrido,ethyl, 2-propenyl, 2-propynyl, propyl,isopropyl, butyl, 2-butyl, (R)-2-butyl,(S)-2-butyl, tert-butyl,isobutyl, 1-pentyl, 3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl,6-amidocarbonylhexyl, 4-methyl-2-pentyl, 3-hydroxypropyl,3-methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl, 3-methyl-2-butyl,2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl, 2-hydroxyethyl,2-amidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl, 4-guanidinobutyl,3-hydroxypropyl, 4-hydroxybutyl, 6-cyanohexyl, 2-dimethylaminoethyl,3-methylbutyl, 2-methylbutyl, (S)-2-methylbutyl, 3-aminopropyl, 2-hexyl,and 4-aminobutyl; A is selected from the group consisting of singlecovalent bond, CH₂, CH₃CH, and CH₂CH₂; M is selected from the groupconsisting of N and R¹—C; R¹ is selected from the group consisting ofhydrido, fluoro, and chloro; R² is selected from the group consisting of5-amino-2-fluorophenyl, 3-amino-2-methylphenyl,5-amino-2-methylthiophenyl, 3-aminophenyl, 3-carboxyphenyl,3-cyanophenyl, 3-methoxycarbonylphenyl, phenyl, and 3-pyridyl; Y⁰ isselected from the group consisting of 5-amidino-2-thienylmethyl,4-amidinobenzyl, 2-fluoro-4-amidinobenzyl, and 3-fluoro-4-amidinobenzyl.24. A compound as recited in claim 17 where said compound is selectedfrom the group having the Formula:

or a pharmaceutically acceptable salt thereof, wherein: R² is3-aminophenyl, B is 2,2,2-trifluoroethyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is CH; R² is 3-aminophenyl, B is (S)-2-butyl, Ais single bond, Y⁰ is 4-amidinobenzyl, and M is CH; R² is5-amino-2-fluorophenyl, B is isopropyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is CH; R² is 2-methyl-3-aminophenyl, B isisopropyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is CH; R² is3-aminophenyl, B is ethyl, A is single bond, Y⁰ is 4-amidinobenzyl, andM is CH; R² is 3-aminophenyl, B is ethyl, A is single bond, Y⁰ is4-amidino-2-fluorobenzyl, and M is CH; R² is 3-aminophenyl, B is2-propenyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is CH; R² is3-aminophenyl, B is isopropyl, A is single bond, Y⁰ is4-amidino-2-fluorobenzyl, and M is CH; p1 R² is 3-aminophenyl, B isisopropyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is CH; R² is3-aminophenyl, B is 2-butyl, A is single bond, Y⁰ is 4-amidinobenzyl,and M is CH; R² is 3-aminophenyl, B is (R)-2-butyl, A is single bond, Y⁰is 4-amidinobenzyl, and M is CH; R² is 3-aminophenyl, B is 2-propynyl, Ais single bond, Y⁰ is 4-amidinobenzyl, and M is CH; R² is 3-aminophenyl,B is 3-pentyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is CH; R²is 3-aminophenyl, B is hydrido, A is CH₂, Y⁰ is 4-amidinobenzyl, and Mis CH; R² is 3-aminophenyl, B is ethyl, A is CH₂, Y⁰ is 4-amidinobenzyl,and M is CH; R² is 3-aminophenyl, B is 2-methypropyl, A is single bond,Y⁰ is 4-amidinobenzyl, and M is CH; R² is 3-aminophenyl, B is 2-propyl,A is CH₃CH, Y⁰ is 4-amidinobenzyl, and M is CH; R² is 3-aminophenyl, Bis propyl, A is single bond, Y⁰ is 4-amidino-2-fluorobenzyl, and M isCH; R² is 3-aminophenyl, B is 6-amidocarbonylhexyl, A is single bond, Y⁰is 4-amidinobenzyl, and M is CH; R² is 3-aminophenyl, B is tert-butyl, Ais single bond, Y⁰ is 4-amidinobenzyl, and M is CH; R² is 3-aminophenyl,B is tert-butyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is CH;R² is 3-aminophenyl, B is 3-hydroxypropyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is CH; R² is 3-aminophenyl, B is 2-methylpropyl,A is single bond, Y⁰ is 4-amidino-2-fluorobenzyl, and M is CH; R² is3-aminophenyl, B is butyl, A is single bond, Y⁰ is 4-amidinobenzyl, andM is CH; R² is 3-aminophenyl, B is 3-methoxy-2-propyl, A is single bond,Y⁰ is 4-amidinobenzyl, and M is CH; R² is 3-aminophenyl, B is3-methoxy-2-propyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M isCH; R² is 3-aminophenyl, B is 2-methoxy-2-ethyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is CH; R² is 3-aminophenyl, B is 2-propyl, A issingle bond, Y⁰ is 5-amidino-2-thienylmethyl, and M is CH; R² is3-aminophenyl, B is 2-propyl, A is single bond, Y⁰ is4-amidino-3-fluorobenzyl, and M is CH; R² is 3-carboxyphenyl, B is2-propyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is CH; R² is3-aminophenyl, B is 2-propyl, A is single bond, Y⁰ is4-amidino-3-fluorobenzyl, and M is CH; R² is 3-aminophenyl, B is2,2,2-trifluoroethyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M isN; R² is 3-aminophenyl, B is (S)-2-butyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is N; R² is 5-amino-2-fluorophenyl, B isisopropyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is N; R² is2-methyl-3-aminophenyl, B is isopropyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is N; R² is 3-aminophenyl, B is ethyl, A issingle bond, Y⁰ is 4-amidinobenzyl, and M is N; R² is 3-aminophenyl, Bis ethyl, A is single bond, Y⁰ is 4-amidino-2-fluorobenzyl, and M is N;R² is 3-aminophenyl, B is 2-propenyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is N; R² is 3-aminophenyl, B is isopropyl, A issingle bond, Y⁰ is 4-amidino-2-fluorobenzyl, and M is N; R² is3-aminophenyl, B is isopropyl, A is single bond, Y⁰ is 4-amidinobenzyl,and M is N; R² is 3-aminophenyl, B is 2-butyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is N; R² is 3-aminophenyl, B is (R)-2-butyl, A issingle bond, Y⁰ is 4-amidinobenzyl, and M is N; R² is 3-aminophenyl, Bis 2-propynyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is N; R²is 3-aminophenyl, B is 3-pentyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is N; R² is 3-aminophenyl, B is hydrido, A isCH₂, Y⁰ is 4-amidinobenzyl, and M is N; R² is 3-aminophenyl, B is ethyl,A is CH₂, Y⁰ is 4-amidinobenzyl, and M is N; R² is 3-aminophenyl, B is2-methypropyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is N; R²is 3-aminophenyl, B is 2-propyl, A is CH₃CH, Y⁰ is 4-amidinobenzyl, andM is N; R² is 3-aminophenyl, B is propyl, A is single bond, Y⁰ is4-amidino-2-fluorobenzyl, and M is N; R² is 3-aminophenyl, B is6-amidocarbonylhexyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M isN; R² is 3-aminophenyl, B is tert-butyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is N; R² is 3-aminophenyl, B is tert-butyl, A issingle bond, Y⁰ is 4-amidinobenzyl, and M is N; R² is 3-aminophenyl, Bis 3-hydroxypropyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is N;R² is 3-aminophenyl, B is 2-methylpropyl, A is single bond, Y⁰ is4-amidino-2-fluorobenzyl, and M is N; R² is 3-aminophenyl, B is butyl, Ais single bond, Y⁰ is 4-amidinobenzyl, and M is N; R² is 3-aminophenyl,B is 3-methoxy-2-propyl, A is single bond, Y⁰ is 4-amidinobenzyl, and Mis N; R² is 3-aminophenyl, B is 3-methoxy-2-propyl, A is single bond, Y⁰is 4-amidinobenzyl, and M is N; R² is 3-aminophenyl, B is2-methoxy-2-ethyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is N;R² is 3-aminophenyl, B is 2-propyl, A is single bond, Y⁰ is5-amidino-2-thienylmethyl, and M is N; R² is 3-aminophenyl, B is2-propyl, A is single bond, Y⁰ is 4-amidino-3-fluorobenzyl, and M is N;R² is 3-carboxyphenyl, B is 2-propyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is N; R² is 3-aminophenyl, B is 2-propyl, A issingle bond, Y⁰ is 4-amidino-3-fluorobenzyl, and M is CH.
 25. Thecompound as recited in claim 2 having the Formula:

or a pharmaceutically acceptable salt thereof, wherein; B is selectedfrom the group consisting of C3-C7 cycloalkyl and C4-C6 saturatedheterocyclyl, wherein each ring carbon is optionally substituted withR³³, a ring carbon other than the ring carbon at the point of attachmentof B to A is optionally substituted with oxo provided that no more thanone ring carbon is substituted by oxo at the same time, ring carbons anda nitrogen adjacent to the carbon atom at the point of attachment areoptionally substituted with R⁹ or R¹³, a ring carbon or nitrogenadjacent to the R⁹ position and two atoms from the point of attachmentis optionally substituted with R¹⁰, a ring carbon or nitrogen adjacentto the R¹³ position and two atoms from the point of attachment isoptionally substituted with R¹², a ring carbon or nitrogen three atomsfrom the point of attachment and adjacent to the R¹⁰ position isoptionally substituted with R¹¹, a ring carbon or nitrogen three atomsfrom the point of attachment and adjacent to the R¹² position isoptionally substituted with R³³, and a ring carbon or nitrogen fouratoms from the point of attachment and adjacent to the R¹¹ and R³³positions is optionally substituted with R³⁴; R⁹, R¹¹, and R¹³ areindependently selected from the group consisting of hydrido, hydroxy,amino, amidino, guanidino, lower alkylamino, alkylthio,alkylsulfonamido, alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkylamidosulfonyl, alkyl, alkoxy, halo, haloalkyl, haloalkoxy, hydroxyalkyl,carboxy, carboxamido, and cyano; R¹⁰ and R¹² are independently selectedfrom the group consisting of hydrido, acetamido, haloacetamido, amidino,guanidino, alkyl, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino,alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, hydroxyalkyl, aminoalkyl, carboalkoxy, carboxy,carboxyalkyl, amidocarbonyl, halo, haloalkyl, and cyano; R³³ and R³⁴ areindependently selected from the group consisting of hydrido, acetamido,haloacetamido, amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino,lower alkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl,dialkyl amidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,carboalkoxy, carboxy, carboxamido, cyano, and Q^(b); A is selected fromthe group consisting of single covalent bond and(CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected from 0through 1, pa is an integer selected from 0 through 3, and W⁷ isselected from the group consisting of (R⁷)NC(O) and N(R⁷); R⁷ isselected from the group consisting of hydrido, hydroxy and alkyl; R¹⁵ isselected from the group consisting of hydrido, halo, alkyl, andhaloalkyl; M is selected from the group consisting of N and R¹—C; R¹ isselected from the group consisting of hydrido, hydroxy, hydroxyamino,amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino,aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo; R²is Z⁰—Q; Z⁰ is selected from the group consisting of a covalent singlebond, O, S, NH, and CH₂; Q is selected from the group consisting of aryland heteroaryl wherein a carbon adjacent to the carbon at the point ofattachment is optionally substituted by R⁹, the other carbon adjacent tothe carbon at the point of attachment is optionally substituted by R¹³,a carbon adjacent to R⁹ and two atoms from the carbon at the point ofattachment is optionally substituted by R¹⁰, a carbon adjacent to R¹³and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹², and any carbon adjacent to both R¹⁰ and R¹² isoptionally substituted by R¹¹; Y⁰ is formula (IV):

 wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one is a covalent bond, K² is C, no more than one of D⁵, D⁶,J⁵, and J⁶ is O, no more than one of D⁵, D⁶, J⁵, and J⁶ is S, one of D⁵,D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ are N; R¹⁶,R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group consistingof hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy,amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl,alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy,hydroxyalkyl, aminoalkyl, and cyano; R¹⁶ and R¹⁹ are optionally Q^(b)with the proviso that no more than one of R¹⁶ and R¹⁹ is Q^(b) at thesame time and that Q^(b) is Q^(be); Q^(b) is selected from the groupconsisting of NR²⁰R²¹, Q^(be) wherein Q^(be) is hydrido, andC(NR²⁵)NR²³R²⁴, with the provisos that no more than one of R²⁰ and R²¹is hydroxy at the same time and that no more than one of R²³ and R²⁴ ishydroxy at the same time; R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independentlyselected from the group consisting of hydrido, alkyl, and hydroxy; Q^(s)is selected from the group consisting of a single covalent bond, CH₂,and CH₂CH₂.
 26. The compound as recited in claim 25 or apharmaceutically acceptable salt thereof, wherein; B is selected fromthe group consisting of cyclopropyl, cyclobutyl, oxetan-3-yl,azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, thiaetan-3-yl, cyclopentyl,cyclohexyl, norbornyl, 7-oxabicyclo[2.2.1]heptan-2-yl,bicyclo[3.1.0]hexan-6-yl, cycloheptyl, 2-morpholinyl, 3-morpholinyl,4-morpholinyl, 1-piperazinyl, 2-piperazinyl, 1-piperidinyl,2-piperidinyl, 3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl,2-pyrrolidinyl, 3-pyrrolidinyl, 2-dioxanyl, 4H-2-pyranyl, 4H-3-pyranyl,4H-4-pyranyl, 4H-pyran-4-one-2-yl, 4H-pyran-4-one-3-yl,2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydropyranyl,3-tetrahydropyranyl, 4-tetrahydropyranyl, 2-tetrahydrothienyl, and3-tetrahydrothienyl, wherein each ring carbon is optionally substitutedwith R³³, ring carbons and a nitrogen adjacent to the carbon atom at thepoint of attachment are optionally substituted with R⁹ or R¹³, a ringcarbon or nitrogen adjacent to the R⁹ position and two atoms from thepoint of attachment is optionally substituted with R¹⁰, and a ringcarbon or nitrogen adjacent to the R¹³ position and two atoms from thepoint of attachment is optionally substituted with R¹²; R⁹, R¹¹, and R¹³are independently selected from the group consisting of hydrido,amidino, guanidino, carboxy, methyl, ethyl, propyl, isopropyl, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, N-methylamino,N,N-dimethylamino, N-ethylamino, methylthio, ethylthio, isopropylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, and cyano; R¹⁰ and R¹² are independentlyselected from the group consisting of hydrido, amidino, guanidino,carboxy, carboxymethyl, methyl, ethyl, propyl, isopropyl, methoxy,ethoxy, isopropoxy, propoxy, hydroxy, amino, methoxyamino, ethoxyamino,acetamido, trifluoroacetamido, aminomethyl, 1-aminoethyl, 2-aminoethyl,N-methylamino, dimethylamino, N-ethylamino, methanesulfonamido,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl,2,2,2-trifluoro-1-hydroxyethyl, methoxycarbonyl, ethoxycarbonyl,amidocarbonyl, N-methylamidocarbonyl, N,N-dimethylamidocarbonyl, fluoro,chloro, bromo, and cyano; R³³ is selected from the group consisting ofhydrido, amidino, guanidino, carboxy, methoxy, ethoxy, isopropoxy,propoxy, hydroxy, amino, methoxyamino, ethoxyamino, acetamido,trifluoroacetamido, N-methylamino, dimethylamino, N-ethylamino,methylthio, ethylthio, isopropylthio, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, 2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl,methoxycarbonyl, ethoxycarbonyl, amidocarbonyl, N-methylamidocarbonyl,N,N-dimethylamidocarbonyl, cyano, and Q^(b); A is selected from thegroup consisting of single covalent bond, NH, N(CH₃), N(OH), CH₂, CH₃CH,CF₃CH, NHC(O), N(CH₃)C(O), C(O)NH, C(O)N(CH₃), CH₂CH₂, CH₂CH₂CH₂,CH₃CHCH₂, and CF₃CHCH₂; M is selected from the group consisting of N andR¹—C; R¹ is selected from the group consisting of hydrido, hydroxy,amino, amidino, hydroxyamino, aminomethyl, 1-aminoethyl, methylamino,dimethylamino, cyano, methyl, ethyl, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, methoxy, hydroxymethyl, 1-hydroxyethyl,2-hydroxyethyl, methoxyamino, methylthio, ethylthio, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, and bromo; R² is Z⁰—Q; Z⁰ isselected from the group consisting of a covalent single bond, O, S, NH,and CH₂; Q is selected from the group consisting of phenyl, 2-thienyl,3-thienyl, 2-furyl, 3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl,4-imidazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl,5-isoxazolyl, 2-pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrazinyl,2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 3-pyridazinyl,4-pyridazinyl, and 1,3,5-triazin-2-yl, wherein a carbon adjacent to thecarbon at the point of attachment is optionally substituted by R⁹, theother carbon adjacent to the carbon at the point of attachment isoptionally substituted by R¹³, a carbon adjacent to R⁹ and two atomsfrom the carbon at the point of attachment is optionally substituted byR¹⁰, a carbon adjacent to R¹³ and two atoms from the carbon at the pointof attachment is optionally substituted by R¹², and any carbon adjacentto both R¹⁰ and R¹² is optionally substituted by R¹¹; Y⁰ is selectedfrom the group consisting of:1-Q^(b)-4-Q^(s)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹benzene,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸-2-R¹⁹pyridine,3-Q^(b)-6-Q^(s)-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine,2-Q^(b)-4-Q^(s)-3-R¹⁶-6-R¹⁸pyrazine, 3-Q^(b)-6-Q^(s)-2-R¹⁸-5-R¹⁸-4-R¹⁹pyridazine, 2-Q^(b)-5-Q^(s)-6-R¹⁷-4R¹⁸pyrimidine,5-Q^(b)-2-Q^(s)-3-R¹⁶-6-R¹⁹pyrimidine,3-Q^(b)-5-Q^(s)-4-R¹⁶-6-2-R¹⁹thiophene,2-Q^(b)-5-Q^(s)-3-R¹⁶-4R¹⁷thiophene, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹furan,2-Q^(b)-5-Q^(s)-3-R¹⁶-4R¹⁷furan, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹pyrrole,2-Q^(b)-5-Q^(s)-3-R¹⁶-4R¹⁷pyrrole, 4-Q^(b)-2-Q^(s)-5-R¹⁹imidazole,2-Q^(b)-4-Q^(s)-5-R¹⁷imidazole, 3-Q^(b)-5-Q^(s)-4-R¹⁶isoxazole,5-Q^(b)-3-Q^(s)-4-R¹⁶isoxazole, 2-Q^(b)-5-Q^(s)-4-R¹⁶pyrazole,4-Q^(b)-2-Q^(s)-5-R¹⁹thiazole, and 2-Q^(b)-5-Q^(s)-4R¹⁷thiazole; R¹⁶,R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group consistingof hydrido, methyl, ethyl, isopropyl, propyl, carboxy, amidino,guanidino, methoxy, ethoxy, isopropoxy, propoxy, hydroxy, amino,aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino,N-ethylamino, methylthio, ethylthio, isopropylthio, trifluoromethylthio,methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethylsulfonyl,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,2,2,3,3,3-pentafluoropropyl, trifluoromethoxy,1,1,2,2-tetrafluoroethoxy, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, N,N-dimethylamidosulfonyl, hydroxymethyl,1-hydroxyethyl, 2-hydroxyethyl, 2,2,2-trifluoro-1-hydroxyethyl, andcyano; R¹⁶ and R¹⁹ are optionally Q^(b) with the proviso that no morethan one of R¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b) isQ^(be); Q^(b) is selected from the group consisting of Q^(be) whereinQ^(be) is hydrido and C(NR²⁵)NR²³R²⁴, with the proviso that no more thanone of R²³ and R²⁴ is hydroxy at the same time; R²³, R²⁴, and R²⁵ areindependently selected from the group consisting of hydrido, methyl,ethyl, and hydroxy; Q^(s) is selected from the group consisting of asingle covalent bond, CH₂ and CH₂CH₂.
 27. The compound as recited inclaim 26 or a pharmaceutically acceptable salt thereof, wherein; B isselected from the group consisting of cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, oxalan-2-yl,2-(2R)-bicyclo[2.2.1]-heptyl, 1-pyrrolidinyl, 1-piperidinyl,1,1-dioxothiolan-3-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl,azetidin-3-yl, 7-oxabicyclo[2.2.1]heptan-2-yl, bicyclo[3.1.0]hexan-6-yl,2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 1-piperazinyl,2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl,4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl,2-dioxanyl, 4H-2-pyranyl, 4H-3-pyranyl, 4H-4-pyranyl,4H-pyran-4-one-2-yl, 4H-pyran-4-one-3-yl, 2-tetrahydrofuranyl,3-tetrahydrofuranyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl,4tetrahydropyranyl, 2-tetrahydrothienyl, and 3-tetrahydrothienyl; A isselected from the group consisting of single covalent bond, CH₂, NHC(O),CH₂CH₂, and CH₂CH₂CH₂; M is selected from the group consisting of N andR¹—C; R¹ is selected from the group consisting of hydrido, hydroxy,amino, amidino, hydroxyamino, aminomethyl, methylamino, cyano, methyl,trifluoromethyl, methoxy, hydroxymethyl, methoxyamino, methylthio,trifluoromethoxy, fluoro, and chloro; R² is Z⁰—Q; Z⁰ is selected fromthe group consisting of a covalent single bond, O, S, NH, and CH₂; Q isselected from the group consisting of 5-amino-3-amidocarbonylphenyl,5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl,5-amino-3-methoxycarbonylphenyl, 3-amidinophenophenyl,3-amino-2-methylphenyl, 5-amino-2-methylthiophenyl, 3-aminophenyl,benzyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl,3-carboxy-5-hydroxyphenyl, 3-carboxymethyl-5-aminophenyl,3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl,2-chlorophenyl, 2,6-dichlorophenyl, 3-cyanophenyl,3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl,2,5-difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl,3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl,3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl,phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl,2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl,3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl; Y⁰ isselected from the group consisting of:1-Q^(b)-4-Q^(s)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹benzene,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸-2-R¹⁹pyridine,3-Q^(b)-6-Q^(s)-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine,3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹thiophene, and2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷thiophene; R¹⁶ and R¹⁹ are independentlyselected from the group consisting of hydrido, amidino, amino,aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro,chloro, and cyano; R¹⁶ and R¹⁹ are optionally Q^(b) with the provisothat no more than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and thatQ^(b) is Q^(be); R¹⁷ and R¹⁸ are independently selected from the groupconsisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino,carboxy, and cyano; Q^(b) is selected from the group consisting ofQ^(be) wherein Q^(be) is hydrido and C(NR²⁵)NR²³R²⁴; R²³, R²⁴, and R²⁵are independently selected from the group consisting of hydrido andmethyl; Q^(s) is CH₂.
 28. The compound as recited in claim 25 having theFormula:

or a pharmaceutically acceptable salt thereof, wherein; B is selectedfrom the group consisting of C3-C7 cycloalkyl and C4-C6 saturatedheterocyclyl, wherein each ring carbon is optionally substituted withR³³, a ring carbon other than the ring carbon at the point of attachmentof B to A is optionally substituted with oxo provided that no more thanone ring carbon is substituted by oxo at the same time, ring carbons anda nitrogen adjacent to the carbon atom at the point of attachment areoptionally substituted with R⁹ or R¹³, a ring carbon or nitrogenadjacent to the R⁹ position and two atoms from the point of attachmentis optionally substituted with R¹⁰, a ring carbon or nitrogen adjacentto the R¹³ position and two atoms from the point of attachment isoptionally substituted with R¹², a ring carbon or nitrogen three atomsfrom the point of attachment and adjacent to the R¹⁰ position isoptionally substituted with R¹¹, a ring carbon or nitrogen three atomsfrom the point of attachment and adjacent to the R¹² position isoptionally substituted with R³³, and a ring carbon or nitrogen fouratoms from the point of attachment and adjacent to the R¹¹ and R³³positions is optionally substituted with R³⁴; R⁹, R¹¹, and R¹³ areindependently selected from the group consisting of hydrido, hydroxy,amino, amidino, guanidino, lower alkylamino, alkylthio, alkoxy,alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkyl amidosulfonyl,alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido,and cyano; R¹⁰ and R¹² are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, amidino, guanidino,alkyl, alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, loweralkylamino, alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl,dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl,carboalkoxy, carboxy, carboxyalkyl, carboxyamido, and cyano; R³³ and R³⁴are independently selected from the group consisting of hydrido,amidino, guanidino, alkoxy, hydroxy, amino, alkoxyamino, loweralkylamino, alkylthio, amidosulfonyl, monoalkyl amidosulfonyl, dialkylamidosulfonyl, alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl,carboalkoxy, carboxy, carboxamido, and cyano; R³³ is optionally Q^(b); Ais selected from the group consisting of single covalent bond and(CH(R¹⁵))_(pa)—(W⁷)_(rr) wherein rr is an integer selected from 0through 1, pa is an integer selected from 0 through 3, and W⁷ is N(R⁷);R⁷ is selected from the group consisting of hydrido and alkyl R¹⁵ isselected from the group consisting of hydrido, halo, alkyl, andhaloalkyl; M is selected from the group consisting of N and R¹—C; R¹ isselected from the group consisting of hydrido, hydroxy, hydroxyamino,amidino, amino, cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino,aminoalkyl, alkylthio, alkoxyamino, haloalkyl, haloalkoxy, and halo; R²is Z⁰—Q; Z⁰ is a covalent single bond; Q is selected from the groupconsisting of aryl and heteroaryl wherein a carbon adjacent to thecarbon at the point of attachment is optionally substituted by R⁹, theother carbon adjacent to the carbon at the point of attachment isoptionally substituted by R¹³, a carbon adjacent to R⁹ and two atomsfrom the carbon at the point of attachment is optionally substituted byR¹⁰, a carbon adjacent to R¹³ and two atoms from the carbon at the pointof attachment is optionally substituted by R¹², and any carbon adjacentto both R¹⁰ and R¹² is optionally substituted by R¹¹; R⁹, R¹¹, and R¹³are independently selected from the group consisting of hydrido,hydroxy, amino, amidino, guanidino, lower alkylamino, alkylthio, alkoxy,alkylsulfinyl, alkylsulfonyl, amidosulfonyl, monoalkylamidosulfonyl,alkyl, halo, haloalkyl, haloalkoxy, hydroxyalkyl, carboxy, carboxamido,and cyano; R¹⁰ and R¹² are independently selected from the groupconsisting of hydrido, acetamido, haloacetamido, amidino, guanidino,alkyl, alkoxy, alkoxyamino, aminoalkyl, hydroxy, amino, loweralkylamino, alkylsulfonamido, amidosulfonyl, monoalkyl amidosulfonyl,dialkyl amidosulfonyl, hydroxyalkyl, aminoalkyl, halo, haloalkyl,carboalkoxy, carboxy, carboxyamido, carboxyalkyl, and cyano; Y⁰ isformula (IV):

 wherein D⁵, D⁶, J⁵, and J⁶ are independently selected from the groupconsisting of C, N, O, S and a covalent bond with the provisos that nomore than one is a covalent bond, K² is C, no more than one of D⁵, D⁶,J⁵, and J⁶ is O, no more than one of D⁵,D⁶,J⁵, and J⁶ is S, one of D⁵,D⁶, J⁵, and J⁶ must be a covalent bond when two of D⁵, D⁶, J⁵, and J⁶are O and S, and no more than four of D⁵, D⁶, J⁵, and J⁶ are N; R¹⁶,R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group consistingof hydrido, amidino, guanidino, carboxy, haloalkylthio, alkoxy, hydroxy,amino, lower alkylamino, alkylthio, alkylsulfinyl, alkylsulfonyl,alkanoyl, haloalkanoyl, alkyl, halo, haloalkyl, haloalkoxy,hydroxyalkyl, aminoalkyl, and cyano; R¹⁶ and R¹⁹ are optionally Q^(b)with the proviso that no more than one of R¹⁶ and R¹⁹ is Q^(b) at thesame time and that Q^(b) is Q^(be); Q^(b) is selected from the groupconsisting of NR²⁰R²¹, Q^(be) wherein Q^(be) is hydrido, andC(NR²⁵)NR²³R²⁴; R²⁰, R²¹, R²³, R²⁴, and R²⁵ are independently selectedfrom the group consisting of hydrido and alkyl; Q^(s) is CH₂.
 29. Thecompound as recited in claim 28 or a pharmaceutically acceptable saltthereof, wherein; B is selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl,oxalan-2-yl, 2-(2R)-bicyclo[2.2.1]-heptyl, 1,1-dioxothiolan-3-yl,oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl,bicyclo[3.1.0]hexan-6-yl, 2-morpholinyl, 3-morpholinyl, 4-morpholinyl,1-piperazinyl, 2-piperazinyl, 1-piperidinyl, 2-piperidinyl,3-piperidinyl, 4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl,3-pyrrolidinyl, 2-dioxanyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl,2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl,2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each ring carbonis optionally substituted with R³³, ring carbons and a nitrogen adjacentto the carbon atom at the point of attachment are optionally substitutedwith R⁹ or R¹³, a ring carbon or nitrogen adjacent to the R⁹ positionand two atoms from the point of attachment is optionally substitutedwith R¹⁰, and a ring carbon or nitrogen atom adjacent to the R¹³position and two atoms from the point of attachment is optionallysubstituted with R¹²; R⁹, R¹¹, and R¹³ are independently selected fromthe group consisting of hydrido, methyl, ethyl, methoxy, ethoxy,hydroxy, amino, N-methylamino, N,N-dimethylamino, methylthio,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro,bromo, amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,carboxy, and cyano; R¹⁰ and R¹² are independently selected from thegroup consisting of hydrido, amidino, amidocarbonyl,N-methylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy,hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxy,carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, trifluoroacetamido, aminomethyl, N-methylamino,dimethylamino, amidosulfonyl, N-methylamidosulfonyl,N,N-dimethylamidosulfonyl, methoxycarbonyl, fluoro, chloro, bromo, andcyano; R³³ is selected from the group consisting of hydrido, amidino,guanidino, methyl, ethyl, methoxy, ethoxy, hydroxy, carboxy, amino,N-methylamino, dimethylamino, methylthio, ethylthio, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo,amidosulfonyl, N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl,cyano, and Q^(b); A is selected from the group consisting of singlecovalent bond, NH, N(CH₃), CH₂, CH₃CH, CH₂CH₂, and CH₂CH₂CH₂; M isselected from the group consisting of N and R¹—C; R¹ is selected fromthe group consisting of hydrido, hydroxy, amino, amidino, hydroxyamino,aminomethyl, methylamino, cyano, methyl, trifluoromethyl, methoxy,hydroxymethyl, methoxyamino, methylthio, trifluoromethoxy, fluoro, andchloro; R² is selected from the group consisting of phenyl, 2-thienyl,2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl, 2-pyridyl,and 3-pyridyl, wherein a carbon adjacent to the carbon at the point ofattachment is optionally substituted by R⁹, the other carbon adjacent tothe carbon at the point of attachment is optionally substituted by R¹³,a carbon adjacent to R⁹ and two atoms from the carbon at the point ofattachment is optionally substituted by R¹⁰, a carbon adjacent to R¹³and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹², and any carbon adjacent to both R¹⁰ and R¹² isoptionally substituted by R¹¹; Y⁰ is selected from the group consistingof: 1-Q^(b)-4-Q^(s)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁷benzene,2-Q^(b)-5-Q^(s)-6-R¹⁷-4-R¹⁸-2-R¹⁹pyridine,2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷thiophene, 3-Q^(b)-6-Q^(s)-2-R¹⁶-5-R¹⁸-4-R¹⁹pyridine, 3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹thiophene,3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹furan, 2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷furan,3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹pyrrole, 2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷pyrrole,4-Q^(b)-2-Q^(s)-5-R¹⁹thiazole, and 2-Q^(b)-5-Q^(s)-4-R¹⁷thiazole; R¹⁶,R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group consistingof hydrido, methyl, ethyl, amidino, guanidino, methoxy, hydroxy, amino,aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino,methylthio, ethylthio, trifluoromethylthio, methylsulfinyl,methylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,trifluoromethoxy, fluoro, chloro, amidosulfonyl, N-methylamidosulfonyl,hydroxymethyl, carboxy, and cyano. Q^(b) is selected from the groupconsisting of NR²⁰R²¹ and C(NR²⁵)NR²³R²⁴, with the proviso that saidQ^(b) group is bonded directly to a carbon atom; R²⁰, R²¹, R²³, R²⁴, andR²⁵ are independently selected from the group consisting of hydrido,methyl, and ethyl; Q^(s) is CH₂.
 30. The compound as recited in claim 29or a pharmaceutically acceptable salt thereof, wherein; B is selectedfrom the group consisting of cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, oxalan-2-yl, 2-(2R)-bicyclo[2.2.1]-heptyl, 1,1-dioxothiolan-3-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl, azetidin-3-yl,1-pyrrolidinyl and 1-piperidinyl; A is selected from the groupconsisting of a single covalent bond, CH₂, NHC(O), CH₂CH₂ and CH₂CH₂CH₂;M is selected from the group consisting of N and R¹—C; R¹ is selectedfrom the group consisting of hydrido, hydroxy, amino, methyl,trifluoromethyl, fluoro, and chloro; R² is selected from the groupconsisting of 3-aminophenyl, 2,6-dichlorophenyl, 2-hydroxyphenyl,5amino-2-thienyl, and 3-thienyl; Y⁰ is selected from the groupconsisting of: 1-Q^(b)-4-Q^(s)-2-R¹⁶-3-R¹⁷-5-R¹⁸-6-R¹⁹ benzene,3-Q^(b)-5-Q^(s)-4-R¹⁶-2-R¹⁹ thiophene, and2-Q^(b)-5-Q^(s)-3-R¹⁶-4-R¹⁷thiophene; R¹⁶ and R¹⁹ are independentlyselected from the group consisting of hydrido, amidino, amino,aminomethyl, methoxy, methylamino, hydroxy, hydroxymethyl, fluoro,chloro, and cyano; R¹⁶ and R¹⁹ are optionally Q^(b) with the provisothat no more than one of R¹⁶ and R¹⁹ is Q^(b) at the same time and thatQ^(b) is Q^(be); R¹⁷ and R¹⁸ are independently selected from the groupconsisting of hydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino,carboxy, and cyano; Q^(b) is selected from the group consisting ofQ^(be) wherein Q^(be) is hydrido and C(NR²⁵)NR²³R²⁴; R²³, R²⁴, and R²⁵are independently selected from the group consisting of hydrido andmethyl; Q^(s) is CH₂.
 31. The compound as recited in claim 30 or apharmaceutically acceptable salt thereof, wherein; B is selected fromthe group consisting of cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, oxalan-2-yl, 2-(2R)-bicyclo[2.2.1]-heptyl,1,1-dioxothiolan-3-yl, oxetan-3-yl, azetidin-1-yl, azetidin-2-yl,azetidin-3-yl, and 1-piperidinyl; A is selected from the groupconsisting of a single covalent bond, CH₂, CH₂CH₂ and CH₂CH₂CH₂; M isselected from the group consisting of N and R¹—C; R¹ is selected fromthe group consisting of hydrido, fluoro, and chloro; R² is selected fromthe group consisting of 3-aminophenyl, 2,6-dichlorophenyl,2-hydroxyhenyl, phenyl, 5-amino-2-thienyl, and 3-thienyl; Y⁰ is selectedfrom the group consisting of 5amidino-2-thienylmethyl, 4-amidinobenzyl,2-fluoro-amidinobenzyl, and 3-fluoro-4-amidinobenzyl.
 32. A compound asrecited in claim 25 where said compound is selected from the grouphaving the Formula:

or a pharmaceutically acceptable salt thereof, wherein: R² is3-aminophenyl, B is cycylopropyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is CH; R² is 3-aminophenyl, B is cyclobutyl, A issingle bond, Y⁰ is 4-amidino-2-fluorobenzyl, and M is CH; R² is3-aminophenyl, B is cyclobutyl, A is single bond, Y is 4-amidinobenzyl,and M is CH; R² is 3-aminophenyl, B is cyclopropyl, A is single bond, Y⁰is 4-amidino-2-fluorobenzyl, and M is CH; R² is 3-aminophenyl, B iscyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is CH; R² is3-aminophenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidino-3-fluorobenzyl, and M is CH; R² is 3-aminophenyl, B iscyclopentyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is CH; R² is5-amino-2-thienyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is CH; R² is 3-aminophenyl, B is cyclopropyl, Ais CH₂, Y⁰ is 4-amidinobenzyl, and M is CH; R² is 3-aminophenyl, B is2-(2R)-bicyclo[2.2.1]-heptyl, A is single bond, Y⁰ is 4-amidinobenzyl,and M is CH; R² is 3-aminophenyl, B is cyclopentyl, A is single bond, Y⁰is 4amidino-2-fluorobenzyl, and M is CH; R² is 3-aminophenyl, B iscyclohexyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CH; R² is3-aminophenyl, B is oxalan-2-yl, A is CH₂, Y⁰ is 4-amidinobenzyl, and Mis CH; R² is phenyl, B is 1-pyrrolidinyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, and M is CH; R² is 3-aminophenyl, B is 1,1-piperidinyl,A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CH; R² is 3-aminophenyl, Bis 1,1-dioxothiolan-3-yl, A is single bond, Y⁰ is 4-amidinobenzyl, and Mis CH; R² is 2-hydroxyphenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is CH; R² is 3-aminophenyl, B is 1-pyrrolidinyl,A is CH₂CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CH; R² is phenyl, B iscyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is CH; R² is3-thienyl, B is cyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl, andM is CH; R² is 2,6-dichlorophenyl, B is cyclobutyl, A is single bond, Y⁰is 4-amidinobenzyl, and M is CH; R² is 3-aminophenyl, B is cycylopropyl,A is single bond, Y⁰ is 4-amidinobenzyl, and M is CF; R² is3-aminophenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidino-2-fluorobenzyl, and M is CF; R² is 3-aminophenyl, B iscyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is CF; R² is3-aminophenyl, B is cyclopropyl, A is single bond, Y⁰ is4amidino-2-fluorobenzyl, and M is CF; R² is 3-aminophenyl, B iscyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is CF; R² is3-aminophenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidino-3-fluorobenzyl, and M is CF; R² is 3-aminophenyl, B iscyclopentyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is CF; R² is5amino-2-thienyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is CF; R² is 3-aminophenyl, B is cyclopropyl, Ais CH₂, Y⁰ is 4-amidinobenzyl, and M is CF; R² is 3-aminophenyl, B is2-(2R)-bicyclo[2.2.1]-heptyl, A is single bond, Y⁰ is 4-amidinobenzyl,and M is CF; R² is 3-aminophenyl, B is cyclopentyl, A is single bond, Y⁰is 4-amidino-2-fluorobenzyl, and M is CF; R² is 3-aminophenyl, B iscyclohexyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CF; R² is3-aminophenyl, B is oxalan-2-yl, A is CH₂, Y⁰ is 4-amidinobenzyl, and Mis CF; R² is phenyl, B is 1-pyrrolidinyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, and M is CF; R² is 3-aminophenyl, B is 1-piperidinyl, Ais CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CF; R² is 3-aminophenyl, B is1,1-dioxothiolan-3-yl, A is single bond, Y⁰ is 4-amidinobenzyl, and M isCF; R² is 2-hydroxyphenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is CF; R² is 3-aminophenyl, B is 1-pyrrolidinyl,A is CH₂CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is CF; R² is phenyl, B iscyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is CF; R² is3-thienyl, B is cyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl, andM is CF; R² is 2,6-dichlorophenyl, B is cyclobutyl, A is single bond, Y⁰is 4-amidinobenzyl, and M is CF; R² is 3-aminophenyl, B is cycylopropyl,A is single bond, Y⁰ is 4-amidinobenzyl, and M is N; R² is3-aminophenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidino-2-fluorobenzyl, and M is N; R² is 3-aminophenyl, B iscyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is N; R² is3-aminophenyl, B is cyclopropyl, A is single bond, Y⁰ is4-amidino-2-fluorobenzyl, and M is N; R² is 3-aminophenyl, B iscyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is N; R² is3-aminophenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidino-3-fluorobenzyl, and M is N; R² is 3-aminophenyl, B iscyclopentyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is N; R² is5-amino-2-thienyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is N; R² is 3-aminophenyl, B is cyclopropyl, A isCH₂, Y⁰ is 4-amidinobenzyl, and M is N; R² is 3-aminophenyl, B is2-(2R)-bicyclo[2.2.1]-heptyl, A is single bond, Y⁰ is 4-amidinobenzyl,and M is N; R² is 3-aminophenyl, B is cyclopentyl, A is single bond, Y⁰is 4-amidino-2-fluorobenzyl, and M is N; R² is 3-aminophenyl, B iscyclohexyl, A is CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is N; R² is3-aminophenyl, B is oxalan-2-yl, A is CH₂, Y⁰ is 4-amidinobenzyl, and Mis N; R² is phenyl, B is 1-pyrrolidinyl, A is CH₂CH₂, Y⁰ is4-amidinobenzyl, and M is N; R² is 3-aminophenyl, B is 1-piperidinyl, Ais CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is N; R² is 3-aminophenyl, B is1,1-dioxothiolan-3-yl, A is single bond, Y⁰ is 4-amidinobenzyl, and M isN; R² is 2-hydroxyphenyl, B is cyclobutyl, A is single bond, Y⁰ is4-amidinobenzyl, and M is N; R² is 3-aminophenyl, B is 1-pyrrolidinyl, Ais CH₂CH₂CH₂, Y⁰ is 4-amidinobenzyl, and M is N; R² is phenyl, B iscyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl, and M is N; R² is3-thienyl, B is cyclobutyl, A is single bond, Y⁰ is 4-amidinobenzyl, andM is N; R² is 2,6dichlorophenyl, B is cyclobutyl, A is single bond, Y⁰is 4-amidinobenzyl, and M is CH.
 33. The compound having the Formula:

or a pharmaceutically acceptable salt thereof, wherein; B is selectedfrom the group consisting of aryl and heteroaryl wherein a carbonadjacent to the carbon at the point of attachment is optionallysubstituted by R³², the other carbon adjacent to the carbon at the pointof attachment is optionally substituted by R³⁶, a carbon adjacent to R³²and two atoms from the carbon at the point of attachment is optionallysubstituted by R³³, a carbon adjacent to R³⁶ and two atoms from thecarbon at the point of attachment is optionally substituted by R³⁵, andany carbon adjacent to both R³³ and R³⁵ is substituted by R³⁴; R³², R³³,R³⁴, R³⁵, and R³⁶ are independently selected from the group consistingof hydrido, acetamido, haloacetamido, amidino, guanidino, alkylenedioxy,haloalkylthio, alkanoyloxy, alkoxy, hydroxy, amino, alkoxyamino,haloalkanoyl, nitro, lower alkylamino, alkylthio, aryl, aralkyl,cycloalkyl, cycloalkylalkyl, heteroaryl, heterocyclyl, alkylsulfonamido,amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl,alkenyl, halo, haloalkyl, haloalkenyl, haloalkoxy, hydroxyalkyl,alkylamino, carboalkoxy, carboxy, carboxamido, cyano, and Q^(b); B isoptionally selected from the group consisting of hydrido, trialkylsilyl,C2-C8 alkyl, C3-C8 alkylenyl, C3-C8 alkenyl, C3-C8 alkynyl, and C2-C8haloalkyl, wherein each member of group B is optionally substituted atany carbon up to and including 6 atoms from the point of attachment of Bto A with one or more of the group consisting of R³², R³³, R³⁴, R³⁵, andR³⁶; B is optionally selected from the group consisting of C3-C12cycloalkyl and C4-C9 saturated heterocyclyl, wherein each ring carbon isoptionally substituted with R³³, a ring carbon other than the ringcarbon at the point of attachment of B to A is optionally substitutedwith oxo provided that no more than one ring carbon is substituted byoxo at the same time, ring carbons and a nitrogen adjacent to the carbonatom at the point of attachment are optionally substituted with R⁹ orR¹³, a ring carbon or nitrogen adjacent to the R⁹ position and two atomsfrom the point of attachment is optionally substituted with R¹⁰, a ringcarbon or nitrogen adjacent to the R¹³ position and two atoms from thepoint of attachment is optionally substituted with R¹², a ring carbon ornitrogen three atoms from the point of attachment and adjacent to theR¹⁰ position is optionally substituted with R¹¹, a ring carbon ornitrogen three atoms from the point of attachment and adjacent to theR¹² position is optionally substituted with R³³, and a ring carbon ornitrogen four atoms from the point of attachment and adjacent to the R¹¹and R³³ positions is optionally substituted with R³⁴; R⁹, R¹⁰, R¹¹, R¹²,and R¹³ are independently selected from the group consisting of hydrido,acetamido, haloacetamido, alkoxyamino, alkanoyl, haloalkanoyl, amidino,guanidino, alkylenedioxy, haloalkylthio, alkoxy, hydroxy, amino, loweralkylamino, alkylthio, alkylsulfinyl, alkylsulfamido, alkylsulfonyl,amidosulfonyl, monoalkyl amidosulfonyl, dialkyl amidosulfonyl, alkyl,halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, carboalkoxy,carboxy, carboxyalkyl, carboxamido, and cyano; A is selected from thegroup consisting of single covalent bond and (CH(R¹⁵))_(pa)—(W⁷)_(rr)wherein rr is an integer selected from 0 through 1, pa is an integerselected from 0 through 3, and W⁷ is selected from the group consistingof O, S, C(O), (R⁷)NC(O), (R⁷)NC(S), and N(R⁷); R⁷ is selected from thegroup consisting of hydrido, hydroxy and alkyl; R¹⁵ is selected from thegroup consisting of hydrido, hydroxy, halo, alkyl, and haloalkyl; M isselected from the group consisting of N and R¹—C; R¹ is selected fromthe group consisting of hydrido, hydroxy, hydroxyamino, amidino, amino,cyano, hydroxyalkyl, alkoxy, alkyl, alkylamino, aminoalkyl, alkylthio,alkoxyamino, haloalkyl, haloalkoxy, and halo; R² is Z⁰—Q; Z⁰ is selectedfrom the group consisting of covalent single bond and (CR⁴¹R⁴²)_(q)wherein q is an integer selected from 1 through 2,(CH(R⁴¹))_(g)—W⁰—(CH(R⁴²))_(p) wherein g and p are integersindependently selected from 0 through 3 and W⁰ is selected from thegroup consisting of O, S, and N(R⁴¹), and(CH(R⁴¹))_(e)—W²²—(CH(R⁴²))_(h) wherein e and h are integersindependently selected from 0 through 1 and W²² is selected from thegroup consisting of CR⁴¹═CR⁴², 1,2-cyclopropyl, 1,2-cyclobutyl,1,2-cyclohexyl, 1,3-cyclohexyl, 1,2-cyclopentyl, 1,3-cyclopentyl,2,3-morpholinyl, 2,4-morpholinyl, 2,6-morpholinyl, 3,4-morpholinyl,3,5-morpholinyl, 1,2-piperazinyl, 1,3-piperazinyl, 2,3-piperazinyl,2,6-piperazinyl, 1,2-piperidinyl, 1,3-piperidinyl, 2,3-piperidinyl,2,4-piperidinyl, 2,6-piperidinyl, 3,4-piperidinyl, 1,2-pyrrolidinyl,1,3-pyrrolidinyl, 2,3-pyrrolidinyl, 2,4-pyrrolidinyl, 2,5pyrrolidinyl,3,4-pyrrolidinyl, 2,3-tetrahydrofuranyl, 2,4-tetrahydrofuranyl,2,5tetrahydrofuranyl, and 3,4-tetrahydrofuranyl, with the proviso thatZ⁰ is directly bonded to the pyrazinone ring; R⁴¹ and R⁴² areindependently selected from the group consisting of hydrido, hydroxy,and amino; Q is selected from the group consisting of hydrido with theproviso that Z⁰ is other than a covalent single bond, aryl andheteroaryl, wherein a carbon adjacent to the carbon at the point ofattachment is optionally substituted by R⁹, the other carbon adjacent tothe carbon at the point of attachment is optionally substituted by R¹³,a carbon adjacent to R⁹ and two atoms from the carbon at the point ofattachment is optionally substituted by R¹⁰, a carbon adjacent to R¹³and two atoms from the carbon at the point of attachment is optionallysubstituted by R¹², and any carbon adjacent to both R¹⁰ and R¹² isoptionally substituted by R¹¹; K is CHR^(4a) wherein R^(4a) is selectedfrom the group consisting of hydrido, hydroxyalkyl, alkyl, alkoxyalkyl,alkylthioalkyl, and haloalkyl; E⁰ is selected from the group consistingof a covalent single bond, C(O)N(H), (H)NC(O), (R⁷)NS(O)₂, andS(O)₂N(R⁷); Y^(AT) is Q^(b)—Q^(s); Q^(s) is (CR³⁷R³⁸)_(b) wherein b isan integer selected from 1 through 4, R³⁷ is selected from the groupconsisting of hydrido, alkyl and haloalkyl, and R³⁸ is selected from thegroup consisting of hydrido, alkyl, haloalkyl, aroyl, and heteroaroylwith the provisos that there is at least one aroyl or heteroaroylsubstituent, that no more than one aroyl or heteroaroyl is bonded to(CR³⁷R³⁸)_(b) at the same time, that said aroyl and said heteroaroyl areoptionally substituted at from one through three of the ring carbonswith a substituent selected from the group consisting of R¹⁶, R¹⁷, R¹⁸,and R¹⁹, that said aroyl and said heteroaroyl are bonded to the CR³⁷R³⁸that is directly bonded to E⁰, that is no more than one alkyl or onehaloalkyl is bonded to a CR³⁷R³⁸ at the same time, and that said alkyland haloalkyl are bonded to a carbon other than the one bonding thearoyl or heteroaroyl; R¹⁶, R¹⁷, R¹⁸, and R¹⁹ are independently selectedfrom the group consisting of hydrido, amidino, guanidino, carboxy,haloalkylthio, alkoxy, hydroxy, amino, alkoxyamino, lower alkylamino,alkylthio, alkylsulfinyl, alkylsulfonyl, alkanoyl, haloalkanoyl, alkyl,halo, haloalkyl, haloalkoxy, hydroxyalkyl, aminoalkyl, and cyano; R¹⁶and R¹⁹ are optionally Q^(b) with the proviso that no more than one ofR¹⁶ and R¹⁹ is Q^(b) at the same time and that Q^(b) is Q^(be); Q^(b) isselected from the group consisting of NR²⁰R²¹, Q^(be) wherein Q^(be) ishydrido, N(R²⁶)C(NR²⁵)N(R²³)(R²⁴), and C(NR²⁵)NR²³R²⁴, with the provisosthat no more than one of R²⁰ and R²¹ is hydroxy, amino, alkylamino, ordialkylamino at the same time and that no more than one of R²³ and R²⁴is hydroxy, amino, alkylamino, or dialkylamino at the same time; R²⁰,R²¹, R²², R²³, R²⁴, and R²⁵ are independently selected from the groupconsisting of hydrido, alkyl, hydroxy, amino, alkylamino anddialkylamino.
 34. The compound as recited in claim 33 having theFormula:

or a pharmaceutically acceptable salt thereof, wherein; B is selectedfrom the group consisting of phenyl, 2-thienyl, 3-thienyl, 2-furyl,3-furyl, 2-pyrrolyl, 3-pyrrolyl, 2-imidazolyl, 4-imidazolyl,3-pyrazolyl, 4-pyrazolyl, 2-thiazolyl, 3-isoxazolyl, and 5-isoxazolyl,wherein a carbon adjacent to the carbon at the point of attachment isoptionally substituted by R³², the other carbon adjacent to the carbonat the point of attachment is optionally substituted by R³⁶, a carbonadjacent to R³² and two atoms from the carbon at the point of attachmentis optionally substituted by R³³, a carbon adjacent to R³⁶ and two atomsfrom the carbon at the point of attachment is optionally substituted byR³⁵, and any carbon adjacent to both R³³ and R³⁵ is optionallysubstituted by R³⁴; R³², R³³, R³⁴, R³⁵, and R³⁶ are independentlyselected from the group consisting of hydrido, amidino, guanidino,methyl, ethyl, methoxy, ethoxy, hydroxy, amino, N-methylamino,dimethylamino, methylthio, ethylthio, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, fluoro, chloro, bromo, amidosulfonyl,N-methylamidosulfonyl, hydroxymethyl, amidocarbonyl, carboxy, cyano, andQ^(b); B is optionally selected from the group consisting of hydrido,ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl, butyl, 2-butenyl,2-butynyl, sec-butyl, tert-butyl, isobutyl, 2-methylpropenyl, 1-pentyl,2-pentenyl, 3-pentenyl, 2-pentynyl, 3-pentynyl, 2-pentyl, 3-pentyl,2-methylbutyl, 2-methyl-2-butenyl, 3-methylbutyl, 3-methyl-2-butenyl,1-hexyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 2-hexynyl, 3-hexynyl,4-hexynyl, 2-hexyl, 1-methyl-2-pentenyl, 1-methyl-3-pentenyl,1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 3-hexyl, 1-ethyl-2-butenyl,1-heptyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 2-heptynyl,3-heptynyl, 4-heptynyl, 5-heptynyl, 2-heptyl, 1-methyl-2-hexenyl,1-methyl-3-hexenyl, 1-methyl-4-hexenyl, 1-methyl-2-hexynyl,1-methyl-3-hexynyl, 1-methyl-4-hexynyl, 3-heptyl, 1-ethyl-2-pentenyl,1-ethyl-3-pentenyl, 1-ethyl-2-pentynyl, 1-ethyl-3-pentynyl,2,2,2-trifluoroethyl, 2,2-difluoropropyl,4-trifluoromethyl-5,5,5-trifluoropentyl, 4-trifluoromethylpentyl,5,5,6,6,6pentafluorohexyl, and 3,3,3-trifluoropropyl, wherein eachmember of group B is optionally substituted at any carbon up to andincluding 5 atoms from the point of attachment of B to A with one ormore of the group consisting of R³², R³³, R³⁴, R³⁵, and R³⁶; B isoptionally selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, oxalan-2-yl,2-(2R)-bicyclo[2.2.1]-heptyl, 1,1-dioxothiolan-3-yl, oxetan-3-yl,azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, bicyclo[3.1.0]hexan-6-yl,2-morpholinyl, 3-morpholinyl, 4-morpholinyl, 1-piperazinyl,2-piperazinyl, 1-piperidinyl, 2-piperidinyl, 3-piperidinyl,4-piperidinyl, 1-pyrrolidinyl, 2-pyrrolidinyl, 3-pyrrolidinyl,2-dioxanyl, 2-tetrahydrofuranyl, 3-tetrahydrofuranyl,2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl,2-tetrahydrothienyl, and 3-tetrahydrothienyl, wherein each ring carbonis optionally substituted with R³³, ring carbons and a nitrogen adjacentto the carbon atom at the point of attachment are optionally substitutedwith R⁹ or R¹³, a ring carbon or nitrogen adjacent to the R⁹ positionand two atoms from the point of attachment is optionally substitutedwith R¹⁰, and a ring carbon or nitrogen adjacent to the R¹³ position andtwo atoms from the point of attachment is optionally substituted withR¹²; R⁹, R¹¹, and R¹³ are independently selected from the groupconsisting of hydrido, methyl, ethyl, methoxy, ethoxy, hydroxy, amino,N-methylamino, N,N-dimethylamino, methylthio, trifluoromethyl,pentafluoroethyl, 2,2,2-trifluoroethyl, fluoro, chloro, bromo,amidosulfonyl, N-methylamidosulfonyl, N,N-dimethylamidosulfonyl,hydroxymethyl, 1-hydroxyethyl, amidocarbonyl, N-methylamidocarbonyl,carboxy, and cyano; R¹⁰ and R¹² are independently selected from thegroup consisting of hydrido, amidino, amidocarbonyl,N-methylamidocarbonyl, guanidino, methyl, ethyl, methoxy, ethoxy,hydroxy, hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, carboxy,carboxymethyl, amino, acetamido, trifluoromethyl, pentafluoroethyl,2,2,2-trifluoroethyl, trifluoroacetamido, aminomethyl, N-methylamino,dimethylamino, amidosulfonyl, N-methylamidosulfonyl,N,N-dimethylamidosulfonyl, methoxycarbonyl, fluoro, chloro, bromo, andcyano; A is selected from the group consisting of single covalent bond,NH, N(CH₃), CH₂, CH₃CH, CH₂CH₂, and CH₂CH₂CH₂; M is selected from thegroup consisting of N and R¹—C; R¹ is selected from the group consistingof hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl,1-aminoethyl, methylamino, dimethylamino, cyano, methyl, ethyl,trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl, methoxy,hydroxymethyl, 1-hydroxyethyl, 2-hydroxyethyl, methoxyamino, methylthio,ethylthio, trifluoromethoxy, 1,1,2,2-tetrafluoroethoxy, fluoro, chloro,and bromo; R² is selected from the group consisting of phenyl,2-thienyl, 2-furyl, 2-pyrrolyl, 2-imidazolyl, 2-thiazolyl, 3-isoxazolyl,2-pyridyl, and 3-pyridyl, wherein a carbon adjacent to the carbon at thepoint of attachment is optionally substituted by R⁹, the other carbonadjacent to the carbon at the point of attachment is optionallysubstituted by R¹³, a carbon adjacent to R⁹ and two atoms from thecarbon at the point of attachment is optionally substituted by R¹⁰, acarbon adjacent to R¹³ and two atoms from the carbon at the point ofattachment is optionally substituted by R¹², and any carbon adjacent toboth R¹⁰ and R¹² is optionally substituted by R¹¹; Y^(AT) isQ^(b)—Q^(s); Q^(s) is selected from the group consisting of:C[R³⁷(benzoyl)](CR³⁷R³⁸)_(b)], C[R³⁷(2-pyridylcarbonyl])](CR³⁷R³⁸)_(b)],C[R³⁷(3-pyridylcarbonyl])](CR³⁷R³⁸)_(b)],C[R³⁷(4-pyridylcarbonyl])](CR³⁷R³⁸)_(b)],C[R³⁷(2-thienylcarbonyl])](CR³⁷R³⁸)_(b)],C[R³⁷(3-thienylcarbonyl])](CR³⁷R³⁸)_(b)],C[R³⁷(2-thiazolylcarbonyl])](CR³⁷R³⁸)_(b)],C[R³⁷(4-thiazolylcarbonyl])](CR³⁷R³⁸)_(b)], andC[R³⁷(5-thiazolylcarbonyl])](CR³⁷R³⁸)_(b)], wherein b is an integerselected from 1 through 3, R³⁷ and R³⁸ are independently selected fromthe group consisting of hydrido, alkyl, and haloalkyl, with the provisosthat said aroyl and said heteroaroyl are optionally substituted at fromone through three of the ring carbons with a substituent selected fromthe group consisting of R¹⁶, R¹⁷, R¹⁸, and R¹⁹ with the proviso that R¹⁷and R¹⁸ are optionally substituted at a carbon selected from other thanthe meta and para carbons relative to the carbonyl of the benzoylsubstituent and the heteroaroyl substituent, that said benzoyl and saidheteroaroyl are bonded to the carbon directly bonded to amide nitrogenof the 1-(amidocarbonymethylene) group, and that is no more than onealkyl or one haloalkyl is bonded to a CR³⁷R³⁸ at the same time; R¹⁶,R¹⁷, R¹⁸, and R¹⁹ are independently selected from the group consistingof hydrido, methyl, ethyl, amidino, guanidino, methoxy, hydroxy, amino,aminomethyl, 1-aminoethyl, 2-aminoethyl, N-methylamino, dimethylamino,methylthio, ethylthio, trifluoromethylthio, methylsulfinyl,methylsulfonyl, trifluoromethyl, pentafluoroethyl, 2,2,2-trifluoroethyl,trifluoromethoxy, fluoro, chloro, amidosulfonyl, N-methylamidosulfonyl,hydroxymethyl, carboxy, and cyano; Q^(b) is selected from the groupconsisting of NR²⁰R²¹ and C(NR²⁵)NR²³R²⁴, with the proviso that saidQ^(b) group is bonded directly to a carbon atom; R²⁰, R²¹, R²³, R²⁴, andR²⁵ are independently selected from the group consisting of hydrido,methyl, and ethyl.
 35. The compound as recited in claim 34 or apharmaceutically acceptable salt thereof, wherein; B is selected fromthe group consisting of 2-aminophenyl, 3-aminophenyl, 3-amidinophenyl,4-amidinophenyl, 3-carboxyphenyl, 3-carboxy-5hydroxyphenyl,3-chlorophenyl, 4-chlorophenyl, 3,4-dichlorophenyl, 2-fluorophenyl,3-fluorophenyl, 3,4-difluorophenyl, 3-hydroxyphenyl, 4-hydroxyphenyl,3-methoxyaminophenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3-methylphenyl,4-methylphenyl, phenyl, 3-trifluoromethylphenyl, 2-imidazoyl, 2-pyridyl,3-pyridyl, 5-chloro-3-trifluoromethyl-2-pyridyl, 4-pyridyl, 2-thienyl,3-thienyl, and 3-trifluoromethyl-2-pyridyl; B is optionally selectedfrom the group consisting of hydrido,ethyl, 2-propenyl, 2-propynyl,propyl, isopropyl, butyl, 2-butyl, (R)-2-butyl,(S)-2-butyl, tert-butyl,isobutyl, 1-pentyl, 3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl,6-amidocarbonylhexyl, 4-methyl-2-pentyl, 3-hydroxypropyl,3-methoxy-2-propyl, 2-methoxyethyl, 2-methyl-2-butyl, 3-methyl-2-butyl,2-dimethylaminopropyl, 2-cyanoethyl, 6-hydroxyhexyl, 2-hydroxyethyl,2-amidinoethyl, 2-guanidinoethyl, 3-guanidinopropyl, 4-guanidinobutyl,3-hydroxypropyl, 4-hydroxybutyl, 6cyanohexyl, 2-dimethylaminoethyl,3-methylbutyl, 2-methylbutyl, (S)-2-methylbutyl, 3-aminopropyl, 2-hexyl,and 4-aminobutyl; B is optionally selected from the group consisting ofcyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, oxalan-2-yl,2-(2R)-bicyclo[2.2.1]-heptyl, 1,1-dioxothiolan-3-yl, oxetan-3-yl,azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, 1-pyrrolidinyl and1-piperidinyl; A is selected from the group consisting of singlecovalent bond, CH₂, CH₃CH, CH₂CH₂, and CH₂CH₂CH₂; M is selected from thegroup consisting of N and R¹—C; R¹ is selected from the group consistingof hydrido, hydroxy, amino, amidino, hydroxyamino, aminomethyl,methylamino, cyano, methyl, trifluoromethyl, methoxy, hydroxymethyl,methoxyamino, methylthio, trifluoromethoxy, fluoro, and chloro; R² isselected from the group consisting of 5-amino-3-amidocarbonylphenyl,5-amino-2-fluorophenyl, 3-amino-5-hydroxymethylphenyl,5-amino-3-methoxycarbonylphenyl, 3-amidinophenyl,3-amino-2-methylphenyl, 5amino-2-methylthiophenyl, 3-aminophenyl,benzyl, 3-carboxyphenyl, 3-carboxy-5-aminophenyl,3-carboxy-5-hydroxyphenyl, 3-carboxymethyl-5aminophenyl,3-carboxymethyl-5-hydroxyphenyl, 3-carboxymethylphenyl, 3-chlorophenyl,2-chlorophenyl, 2,6-dichlorophenyl, 3-cyanophenyl,3-dimethylaminophenyl, 2-fluorophenyl, 3-fluorophenyl,2,5difluorophenyl, 2-hydroxyphenyl, 3-hydroxyphenyl,3-methanesulfonylaminophenyl, 2-methoxyphenyl, 3-methoxyphenyl,3-methoxyaminophenyl, 3-methoxycarbonylphenyl, 2-methylaminophenyl,3-methylaminophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl,phenyl, 3-trifluoroacetamidophenyl, 3-trifluoromethylphenyl,2-trifluoromethylphenyl, 5-amino-2-thienyl, 5-amino-3-thienyl,3-bromo-2-thienyl, 3-pyridyl, 4-pyridyl, 2-thienyl, and 3-thienyl;Y^(AT) is Q^(b)—Q^(s); Q^(s) is selected from the group consisting of:[CH(benzoyl)](CH₂)_(b), [CH(2-pyridylcarbonyl)](CH₂)_(b),[CH(3-pyridylcarbonyl)](CH₂)_(b), [CH(4-pyridylcarbonyl)](CH₂)_(b),[CH(2-thienylcarbonyl)](CH₂)_(b), [CH(3-thienylcarbonyl)](CH₂)_(b),[CH(2-thiazolylcarbonyl)](CH₂)_(b), [CH(4-thiazolylcarbonyl)](CH₂)_(b),and [CH(5thiazolylcarbonyl)](CH₂)_(b). wherein b is an integer selectedfrom 1 through 3, with the provisos that said aroyl and said heteroaroylare optionally substituted at from one through three of the ring carbonswith a substituent selected from the group consisting of R¹⁶, R¹⁷, R¹⁸,and R¹⁹ with the proviso that R¹⁷ and R¹⁸ are optionally substituted ata carbon selected from other than the meta and para carbons relative tothe carbonyl of the benzoyl substituent and the heteroaroyl substituent,and that said benzoyl and said heteroaroyl substituent are bonded to thecarbon directly bonded to amide nitrogen of the1-(amidocarbonymethylene) group; R¹⁶ and R¹⁹ are independently selectedfrom the group consisting of hydrido, amidino, amino, aminomethyl,methoxy, methylamino, hydroxy, hydroxymethyl, fluoro, chloro, and cyano;R¹⁷ and R¹⁸ are independently selected from the group consisting ofhydrido, fluoro, chloro, hydroxy, hydroxymethyl, amino, carboxy, andcyano; Q^(b) is C(NR²⁵)NR²³R²⁴; R²³, R²⁴, and R²⁵ are independentlyselected from the group consisting of hydrido and methyl.
 36. Thecompound as recited in claim 35 or a pharmaceutically acceptable saltthereof, wherein; B is selected from the group consisting of3-aminophenyl, 3-amidinophenyl, 4-amidinophenyl, 3-chlorophenyl,4-chlorophenyl, 3,4-dichlorophenyl, 2-fluorophenyl, 4-methylphenyl,phenyl, 2-imidazoyl, 3-pyridyl, 4-pyridyl, and3-trifluoromethyl-2-pyridyl; B is optionally selected from the groupconsisting of hydrido,ethyl, 2-propenyl, 2-propynyl, propyl, isopropyl,butyl, 2-butyl, (R)-2-butyl,(S)-2-butyl, tert-butyl, isobutyl, 1-pentyl,3-pentyl, 2-methylbutyl, 2,2,2-trifluoroethyl, 6-amidocarbonylhexyl,4-methyl-2-pentyl, 3-hydroxypropyl, 3-methoxy-2-propyl, 2-methoxyethyl,2-methyl-2-butyl, 3-methyl-2-butyl, 2-dimethylaminopropyl, 2-cyanoethyl,6-hydroxyhexyl, 2-hydroxyethyl, 2-amidinoethyl, 2-guanidinoethyl,3-guanidinopropyl, 4-guanidinobutyl, 3-hydroxypropyl, 4-hydroxybutyl,6-cyanohexyl, 2-dimethylaminoethyl, 3-methylbutyl, 2-methylbutyl,(S)-2-methylbutyl, 3-aminopropyl, 2-hexyl, and 4-aminobutyl; B isoptionally selected from the group consisting of cyclopropyl,cyclobutyl, cyclopentyl, cyclohexyl, oxalan-2-yl,2-(2R)-bicyclo[2.2.1]-heptyl, 1,1-dioxothiolan-3-yl, oxetan-3-yl,azetidin-1-yl, azetidin-2-yl, azetidin-3-yl, and 1-piperidinyl; A isselected from the group consisting of a single covalent bond, CH₂,CH₂CH₂ and CH₂CH₂CH₂; M is selected from the group consisting of N andR¹—C; R¹ is selected from the group consisting of hydrido, hydroxy,amino, methyl, trifluoromethyl, fluoro, and chloro; R² is selected fromthe group consisting of 3-aminophenyl, benzyl, 2,6-dichlorophenyl,5-amino-2-thienyl, 5-amino-2-fluorophenyl, 3-amino-2-methylphenyl,5-amino-2-methylthiophenyl, 3-carboxyphenyl, 3-cyanophenyl,3-chlorophenyl, 2-hydroxyhenyl, 3-hydroxyphenyl,3-methanesulfonylaminophenyl, 3-methoxycarbonylphenyl,3-dimethylaminophenyl, 3-methylaminophenyl, 2-methylphenyl,3-methylphenyl, phenyl, 3-pyridyl, 3-trifluoroacetamidophenyl,3-bromo-2-thienyl, 2-thienyl, and 3-thienyl; Y^(AT) is selected from thegroup consisting of 5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl,5-guanidino-1-oxo-1-(4-thiazolyl)-2-pentyl,5-guanidino-1-oxo-1-(5thiazolyl)-2-pentyl,5-guanidino-1-oxo-1-(4-amino-2-thiazolyl)-2-pentyl, and5-guanidino-1-oxo-1-phenyl-2-pentyl.
 37. A compound as recited in claim33 where said compound is selected from the group having the Formula:

or a pharmaceutically acceptable salt thereof, wherein: R² is3-aminophenyl, B is phenyl, A is CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CH; R² is phenyl, Bis phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CH; R² is benzyl, Bis phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CH; R² is phenyl, Bis phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CH; R² is benzyl, Bis phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CH; R² is phenyl, Bis phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CH; R² is3-aminophenyl, B is phenyl, A is CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CF; R² is phenyl, Bis phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CF; R² is benzyl, Bis phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CF; R² is phenyl, Bis phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CF; R² is benzyl, Bis phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CF; R² is phenyl, Bis phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CF; R² is3-aminophenyl, B is phenyl, A is CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CCl; R² is phenyl,B is phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CCl; R² is benzyl,B is phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CCl; R² is phenyl,B is phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CCl; R² is benzyl,B is phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CCl; R² is phenyl,B is phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is CCl; R² is3-aminophenyl, B is phenyl, A is CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is N; R² is phenyl, Bis phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is N; R² is benzyl, Bis phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is N; R² is phenyl, Bis phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is N; R² is benzyl, Bis phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is N; R² is phenyl, Bis phenyl, A is CH₂CH₂, Y^(AT) is5-guanidino-1-oxo-1-(2-thiazolyl)-2-pentyl, and M is N;
 38. Acomposition for inhibiting thrombotic conditions in blood comprising acompound of claim 1 and a pharmaceutically acceptable carrier.
 39. Amethod for inhibiting thrombotic conditions in blood comprising addingto blood a therapeutically effective amount of a composition of claim38.
 40. A method for inhibiting formation of blood platelet aggregatesin blood comprising adding to blood a therapeutically effective amountof a composition of claim
 38. 41. A method for inhibiting thrombusformation in blood comprising adding to blood a therapeuticallyeffective amount of a composition of claim
 38. 42. A method for treatingor preventing venuous thromboembolism and pulmonary embolism in a mammalcomprising administering to the mammal a therapeutically effectiveamount of a composition of claim
 38. 43. A method for treating orpreventing deep vein thrombosis in a mammal comprising administering tothe mammal a therapeutically effective amount of a composition of claim38.
 44. A method for treating or preventing cardiogenic thromboembolismin a mammal comprising administering to the mammal a therapeuticallyeffective amount of a composition of claim
 38. 45. A method for treatingor preventing thromboemboli stroke in humans and other mammalscomprising administering to the mammal a therapeutically effectiveamount of a composition of claim
 38. 46. A method for treating orpreventing thrombosis associated with cancer and cancer chemotherapy inhumans and other mammals comprising administering to the mammal atherapeutically effective amount of a composition of claim
 38. 47. Amethod for treating or preventing unstable angina in humans and othermammals comprising administering to the mammal a therapeuticallyeffective amount of a composition of claim
 38. 48. A method forinhibiting thrombus formation in blood comprising adding to blood atherapeutically effective amount of a compound of claim 1 with atherapeutically effective amount of fibrinogen receptor antagonist.